hplc analysis of acetaminophen

7/28/2019 HPLC Analysis of Acetaminophen

1/26

AcetaminophenMolecular formula: C8H9NO2Molecular weight: 151.2CAS Registry No.: 103-90-2

SAMPLEMatrix: bile, blood, tissue, urineSample preparat ion: Tissue. M acerate 2 g t issue w ith 5 mL water, add 15 mL M eCN, add0.1 mL 1 mg/mL 2-acetamidophenol in ethano l, shak e, centrifuge at 5200 g. Transfersupernatant to 50 mL tube containing 8 mL diethyl ether +12 mL dichloromethane + 1mL citrate buffer, vortex, proceed as in (A). Bile. 2 mL Bile + 3 mL water, add 15 mLMeCN, add 0.1 mL 1 mg/mL 2-acetamidophenol in ethanol, vortex, add 8 mL diethyl ethe r+ 12 mL dich lorom ethan e, vortex, centrifuge at 5200 g, proceed as in (A). Blood, ur in e.5 mL Blood or urine + 15 mL acetone + 0.1 mL 1 mg/mL 2-acetamidophenol in ethanol,vortex for a few s, add 8 mL diethyl e ther, vortex, centrifuge 5200 g. Transfer su pe rn ata ntto 50 mL tube, add 12 mL dichloromethane, add 1 mL citrate buffer, vortex, proceed asin (A). (A). Discard lower, aqueous layer. Filter the organic layer through 3 g florisil + 8g anhydrous sodium sulfate and wash through with 15 mL diethyl ether. Evaporate fil-tr at e to dryne ss un der a stre am of air a t 40. Reco nstitute in 5 mL M eCN : 0.1 N NaH 2PO 460:40 + 3 mL hexane, vortex. Remove and discard upper hexane layer, add 8 mL 20%(v/v) isopropanol in chloroform to the aqueous layer, vortex. Remove and discard the upperaqueous layer a nd ev apora te lower layer. Recon stitute residue in MeCN : w ater 10:9 0,inject an aliquot. (Citrate buffer was saturated sodium citrate containing enough sodiumtunstate (sic) to bring pH to 8. To each 1 L of diethyl ether 10 mL of water and 1 mL ofcitrate buffer are added.)

HPLCVARIABLESColumn: 100 X 4.6 C18 microboreMobile phase: M eCN: dilute phosphoric acid (1 mL 85% phosphoric acid in 140 mL wa ter)7:93Column tem pera ture: 40Flow rate: 0.3Detector: UV 271CHROMATOGRAMRetent ion t ime: 2 .4Internal s tandard: 2-acetamidophenol (4.9)Limit of detect ion: 50 (blood, urine),200 (bile, tissue) ng/mLOTHER SUBSTANCESExtracted: theophyllineKEYWORDSliverREFERENCEMathis, D.F.; Budd, R.D. Extraction of acetaminophen and theophylline from post-mortem tissues andurine for high-performance liquid chromatographic analysis. J.Chromatogr., 1988, 439, 4 6 6 - 4 6 9SAMPLEMatrix: bloodSample preparat ion: 500 |JLL Plasma + 25 |xL 40 (xg/mL 3-acetamidophenol, extract witheth er: dichloromethan e: isopropanol 59 : 40 : 1 . Remove the organic layer and evaporate it


2/26

to dryness under a stream of nitrogen, reconstitute the residue in 250 jxL mobile phase,inject an aliquot.HPLCVARIABLESColumn: 100 X 4.6 microsphere C18 (Chrompack)Mobile phase: MeOH: 50 mM pH 7.8 sodium phosphate buffer 4:96Flow rate: 1Detector: UV 278CHROMATOGRAMInternal standard: 3-acetamidophenolKEYWORDSplasma; pig; pharmacokineticsREFERENCEMonshouwer, M.; Witkamp, R.F.; Nijmeijer, S.M.; Pijpers, A.; Verheijden, J.H.M.; Van Miert,A.S.J.P.A.M. Selective effects of a bacterial infection (Actinobacillus pleuropneumoniae) on the he-patic clearance of caffeine, antipyrine, paracetamol, and indocyanine green in the pig. Xenobiotica,1 9 9 5 , 2 5 , 4 9 1 - 4 9 9SAMPLEMatrix: bloodSample preparation: 100 |xL Plasma + 1 |xg p-anisamide + 1 mL 500 mM pH 7.4Na2HPO4ZKH2PO4 buffer + 1 mL ethyl acetate , shake for 10 min, centrifuge at 1300 g for

5 min. Evaporate the supernatant to dryness under reduced pressure, reconstitute theresidue in 200 |xL mobile phase, inject a 100 |xL aliquot.HPLCVARIABLESColumn: 150 X 4 Nucleosil 7C18Mobile phase: MeCN : 1 % acetic acid 10:90Flow rate: 1.5Injection volum e: 100Detector: UV 254CHROMATOGRAMInternal standard: p-anisamideLimit of detection: 100 ng/mLOTHER SUBSTANCESExtracted: sulfapyridineKEYWORDSplasma; dog; pharmacokineticsREFERENCESagara, K.; Mizuta, H.; Ohshiko, M.; Shibata, M.; Haga, K. Relationship between the phasic period ofinterdigestive migrating contraction and the systemic bioavailability of acetaminophen in dogs.Pharm.Res., 1995, 12, 594-598SAMPLEMatrix: bloodSample preparation: 0.5 mL Plasm a H- 25 |xL 40 jxg/mL 3-acetamidophenol extracted withether: dichloromethane: isopropanol 60:40:1. Evaporate organic layer under a stream ofnitrogen and take up residue in 50 mM pH 7.8 phosphate buffer, inject an aliquot.


3/26

HPLCVARIABLESColumn: 100 X 4.6 Chrompack microsphere C18M obi le phase: Gradient. A was 50 mM pH 7.8 pho sphate buffer. B w as M eOH: 50 mM pH7.8 phosphate buffer 50:50. A:B from 100:0 to 50:50 over 38 min, maintain at 50:50 for2 min.Flow rate: 0 .7Inject ion vo lum e: 250Detector: UV 254CHROMATOGRAMInternal s tandard: 3-acetamidophenolOTHER SUBSTANCESExtracted: metabolites, antipyrineKEYWORDSplasma; pig; pharm acokineticsREFERENCEMonshouwer, M.; Witkamp, R.F.; Pijpers, A.; Verheijden, J.H.M.; Van Miert, A.S.J.P.A.M. Dose-depen-dent pharmacokinetic interaction between antipyrine and paracetamol in vivo and in vitro whenadministered as cocktail in pig. Xenobiotica, 1994, 24, 3 4 7 - 3 5 5SAMPLEMatrix: bloodSample preparat ion: 100 |xL Serum + 100 |xL buffer + 1 . 5 mL IS in 5% isopropanol in

chloroform, vortex for 30 s, centrifuge. Remove the organic layer and evaporate it todryness under a stream of air at room temperature, reconstitute the residue in 100 jxLmobile phase, inject a 6-10 |xL aliquot. (Buffer was 13.6 g KH 2PO 4 in 90 mL water, pHadjusted to 6.8 with about 3 mL 10 M NaOH, made up to 100 mL.)HPLCVARIABLESGuard co lum n: 20 X 4.6 Supelguard LC-I (Supelco)Column: 250 X 4.6 5 |xm Supelcosil LC-I (Supelco)Mobile phase: M eOH :MeC N:buffer 17.5 :17.5 :65 (Buffer wa s 2.72 g KH 2PO 4 in 1.9 L wa-ter, pH adjusted to 6.3 with a bout 2 mL 1 M NaO H, m ade up to 2 L.)Flow rate: 2Inject ion volume: 6-10Detector: UV 273CHROMATOGRAMRetent ion t ime: 2.09Internal s tandard: 3-isobutyl-l-methylxanthine (3.15)OTHER SUBSTANCESExtracted: amobarbital, barbital, caffeine, carbamazepine, chloramphenicol, ethosuximide,mephobarbital, methsuximide, pentobarbital, phenobarbital, phenytoin, primidone, seco-

barbital, theophylline, thio pentalAlso analyzed: acetanilide, butabarbital, butalbital, cimetidine, cyheptamide, diazoxide,diflunisal, disopyramide, ethchlorvynol, glutethimide, heptabarbital, hexobarbital, ibu-profen, indomethacin, ketoprofen, mefenamic acid, mephenytoin, methaqualone, meth-suximide, methyl salicylate, methyprylon, naproxen, nirvanol, phenacetin, phensuximide,phenylbutazone, salicylamide, sulindac, tolmetinNoninterfering: N-acetylcysteine, N-acetylprocainamide, amikacin, ampicillin, aspirin,chlorpropamide, codeine, diphylline, gentamicin, gentisic acid, meprobamate, morphine,netilmicin, procainamide, quinidine, salicylic acid, sulfamethoxazole, tetracycline, tobra-mycin, trimethoprim, valproic acid, vancomycinInterfering: oxphenylbutazone


4/26

KEYWORDSserumREFERENCEMeatherall, R.; Ford, D. Isocratic liquid chromatographic determination of theophylline, acetaminophen,chloramphenicol, caffeine, anticonvulsants, and barbiturates in serum. Ther.Drug M onit., 1988, 10,

101-115SAMPLEMatrix: bloodSample preparat ion: Activate a 1 mL Bond-Elut C8 SPE cartridge with 2 mL MeOH the n1 mL 10 mM HCl, do not allow it to dry completely. Sonicate 1 mL whole blood for 20-30min then apply to cartridge. Wash with 100 |JIL water, elute with three 500 JJLL portionsof MeOH: M eCN: 1% aqueous amm onium hydroxide 50 :20 :30 , combine eluents and evap-orate to dryne ss un de r a s trea m of nitrogen at 40. Redissolve in 1 mL MeOH , inject a20 |JLL aliquot.HPLCVARIABLESColumn: 250 X 4.5 5 |xm Spherisorb ODSMobile phase: M eCN : M eOH : buffer 35 :13 :52 (Buffer w as wa ter adjusted to pH 3.2 w ithorthophosphoric acid.)Flow rate: 1Inject ion volum e: 20Detector: UV 250CHROMATOGRAMRetent ion t ime: 2 .5OTHER SUBSTANCESSimul taneous: ketoprofen, salicylic acid, naproxen, fenoprofen, ibuprofen, indomethacinKEYWORDSwhole blood; SPEREFERENCEMoore, CM.; Tebbett, LR. Rapid extraction of anti-inflammatory drugs in whole blood for HPLC anal-ysis. Forensic Sci.Int, 1987, 34, 155-158SAMPLEMatrix: bloodSample preparat ion: 500 |xL Pla sm a H- 75 (xL water, mix , inject a 20 \xL aliquot directly.HPLCVARIABLESGuard co lumn: 23 X 3.9 37-50 ^m Bondapak C18/CorasilColumn: 300 x 3.9 10 |xm ixBondapak C18Mobile phase: 50 mM pH 6.0 phosphate bufferFlow rate: 2.5Inject ion volum e: 20Detector: UV 254CHROMATOGRAMRetent ion t ime: 18Internal s tandard: acetaminophenOTHER SUBSTANCESExtracted: uric acid, oxipurinol, allopurinol


5/26

KEYWORDSplasma; renew guard column after 50-70 injections; acetaminophen is ISREFERENCENissen, P. Simultaneous determination of allopurinol, oxipurinol and uric acid in human plasma byhigh-performance liquid chromatography. J.Chromatogr., 1982, 228, 382-386SAMPLEMatrix: bloodSample preparat ion: 50 |xL Serum + 50 /ULL 100 mM HCl + 50 (xL 15 jutg/mL p-hydroxy-ethyltheophylline in MeCN + 3 mL ethyl acetate, mix for 30 s, centrifuge at 3000 g for3 min. Remove the organic layer and evaporate it to dryness under a stream of nitrogen,reconstitute the residue in 50 |xL MeOH, inject a 20 |xL aliquot.HPLCVARIABLESColumn: ixBondapak C18Mobile phase: MeCN:buffer 9.75:90.25 (Buffer was 100 mM KH 2PO 4 adjusted to pH 4.0with phosphoric acid.) (At the end of each day clean column with water for 20 min andMeOH for 30 min.)Flow rate: 2Inject ion volume: 20Detector: UV 254CHROMATOGRAMRetent ion t ime: 4 .3Internal s tandard: p-hydroxyethyltheophylline (5.8)Limit of detect ion: 500 ng/mLOTHER SUBSTANCESSimul taneous: dyphylline, theophylline, caffeine, aspirin, salicylic acid, procainamide, N-acetylprocainamideNoninterfering: benzoic acidKEYWORDSserumREFERENCEOu, C-N.; Frawley, V.L. Theophylline, dyphylline, caffeine, acetaminophen, salicylate, acetylsalicylate,procainamide, and N-acetylprocainamide determined in serum with a single liquid-chromatographicassay. Clin.Chem., 1982, 28, 2157-2160SAMPLEMatrix: bloodSample preparat ion: 200 |xL Serum + 200 |xL 50 |xg/mL hexobarbital in MeCN + 25 |xLglacial acetic acid, vortex for 10 s, centrifuge for 1 min, inject a 30-100 |xL aliquot of thesupernatant .HPLCVARIABLESColumn: jxBondapak C18Mobile phase: Grad ient. M eCN : 7.5 g/L N aH 2PO 4 adjusted to pH 3.2 with p hosphoric acid5:95 to 22:78 over 24 min, to 45:55 over 10 min, maintain at 45:55 for 5 min. Re-equilibrate with 5:95 for 5 min.Column temperature: 50Flow rate: 3


6/26

Inject ion vo lum e: 30-100Detector: UV 210CHROMATOGRAMRetent ion t ime: 3 .3Internal s tandard: hexobarbital (20.6)Limit of detect ion: 200-2000 ng/mLOTHER SUBSTANCESExtracted: amobarbital, butabarbital, butalbital, chlordiazepoxide, diazepam, ethchlorvy-nol, flurazepam, glutethimide, methaqualone, methyprylon, nitrazepam, pentobarbital,phenobarbital, phenytoin, primidone, salicylic acid, secobarbital, theophyllineSimul taneous: am itriptyline, caffeine, clomipram ine, codeine, desip ram ine, ethotoin, imip-ramine, lidocaine, mesantoin, methsuximide, nirvanol, nortriptyline, oxazepam, propran-olol, quinidineInterfering: procainamide, phenylpropanolamineKEYWORDSserumREFERENCEKabra, P.M.; Stafford, B.E.; Marton, L.J. Rapid method for screening toxic drugs in serum with liquidchromatography. J.Anal.ToxicoL, 1981, 5, 177 -182SAMPLEMatrix: blood, CSF, gastric fluid, urineSample preparat ion: 200 |xL Serum , urin e, CSF, or gastric fluid + 300 |xL reag ent. Flu shcolumn A to waste w ith 500 |xL 500 mM am mo nium sulfate, inject sa mp le onto columnA, flush column A to was te w ith 500 |xL 500 mM amm onium sulfate, backflush th e con-ten ts of column A onto column B w ith m obile phas e, mo nitor the effluent from column B.(Reagent was 8.05 M guanidine hydrochloride and 1.02 M ammonium sulfate in water.)HPLCVARIABLESColumn: A 40 jim preparative grade C18 (Analytichem); B 75 X 2.1 pellicular C18 (What-man) + 250 x 4.6 5 |xm C8 end-capped (Whatman)Mobile phase: Gradient. A was 50 mM pH 4.5 KH 2PO 4. B was MeCN:isopropanol 80:20.

A:B 90:10 for 1 min, to 30:70 over 20 min.Column temperature: 50F low rate: 1.5Detector: UV 220CHROMATOGRAMRetent ion t ime: 4.93Internal s tandard: heptanophenone (19)OTHER SUBSTANCESExtracted: allobarbital, azinphos, barbital, brallobarbitone, bromazepam, butethal, caf-feine, carbamazepine, carbaryl, cephaloridine, chloramphenicol, chlordiazepoxide, chlo-rothiazide , chlorvinphos, clothiapine, cocaine, coomassie blue, desipr am ine, diazep am , di-phenhydramine, dipipanone, ethylbromphos, flufenamic acid, formothion, griseofulvin,indomethacin, lidocaine, lorazepam, malathion, medazepam, midazolam, oxazepam, par-aoxon, penicillin G, pentobarbital, prazepam, propoxyphene, prothiophos, quinine, sali-cylic acid, secobarbital, strychnine, sulfamethoxazole, theophylline, thiopental, thiorida-zine, trimethoprimKEYWORDSserum; column-switching


7/26

REFERENCEKruger, RB .; Albrecht, C R D e V.; J aars veld , P.P. Use of gua nidin e hydrochloride and am mo nium sulfatein comprehensive in-line sorption enrichment of xenobiotics in biological fluids by high-performanceliquid chromatography. J.Chromatogr., 1993, 612, 191-198

SAMPLEMatrix: blood, salivaSample preparat ion: 500 (xL Saliva or plasm a + 100 JJLL 100 |xg/mL o-hydroxyacetanilide+ 5 mL ethy l aceta te, sha ke for 15 min, centrifuge at 2500 rpm for 5 min . Remove 4 mLof the organic layer and evaporate it to dryness under a stream of nitrogen at 50, recon-stitute the residue in 200 |xL mobile phase, inject a 50 |xL aliquot.HPLCVARIABLESColumn: 150 X 4 Inertsil ODS-2Mobile phase: M eOH : 1.5% acetic acid 15:85 (plasma) or M eOH : M eCN : 50 mM pr j 2.5

potassium phosphate buffer 8:7:85 (saliva)Column temperature: 50Flow rate: 1Inject ion vo lume: 50Detector: UV 240CHROMATOGRAMRetent ion t ime: 4.7 (plasma), 4.0 (saliva)Internal s tandard: o-hydroxyacetanilide (9.9 (plasma), 8.0 (saliva))Limit of quant i tat ion: 100 ng/mLKEYWORDSplasma; human; dog; pharmacokineticsREFERENCEKatori, N.; Aoyagi, N.; Terao, T. Estimation of agitation intensity in the GI tract in humans and dogsbased on in vitro/in vivo correlation. Pharm.Res., 1995, 12, 2 3 7 - 2 4 3SAMPLEMatrix: blood, saliva, urineSample preparat ion: 900 |xL Pla sm a or saliva + 10 jxL 10 |xg/mL 3-acetam inoph en in 30%perchloric acid, mix, centrifuge at 3000 rpm for 15 min, inject an aliquot of thesuperna tantHPLCVARIABLESGuard co lumn: 50 X 4.6 37-53 jim pellicular ODS (Whatman)Column: 250 X 4.6 5 fxm Spherisorb ODS2Mobile phase: M eCN : 20 mM orthophosphoric acid 4 :96 , pH 3.5 (urine) or M eOH : M eCN :20 mM orthophosphoric acid 2:4:94, adjusted to pH 3.2 (plasma) or MeCN:20 mM or-thophosphoric acid 6:94 (saliva)Column tem pera ture: 25Detector: UV (wavelength not specified)CHROMATOGRAMRetent ion t ime: 8.3 (urine), 6.6 (plasma), 6.0 (saliva)Internal s tandard: 3-acetaminophen (12.1 (urine), 9.3 (plasma), 8.3 (saliva))Limit of detect ion : 200 ng/mLKEYWORDSplasma; pharmacokinetics


8/26

REFERENCEAl-Obaidy, S.S.; Po, A.L.W.; McKiernan, RJ.; Glasgow, J.F.T.; Millership, J. Assay of paracetamol andits metabolites in urine, plasma and saliva of children with chronic liver disease. J.Pharm.BiomedAnaL, 1995, 13, 1033-1039

SAMPLEMatrix: blood, urineS a m p l e p r e p a r a t i o n : 200 JJLL Plasma or urine spiked with p-hydroxyethyltheophylline +200 |xL 1 M tetrab utyla m m oniu m dihydrogen phosp hate + 0.2 g potas sium sulfate, mix1 m in, add 3 mL chloroform: isopropanol 1:1 , mix 1 m in, centrifuge 5 m in 2500 g. Remove2 mL of organic layer, evaporate to dryness at 35 under stream of nitrogen, take up in200 |xL mobile phase by mixing for 1 min, inject an aliquot.HPLC VARIABLESC o lu m n: 150 X 4 5 |xm C18 (FSA Laboratory Supplies, Loughborough)M ob ile p h a s e : M eOH: 1% acetic acid containing 0.5 mM tetrabutylam m onium dihydrogen-phosphate and 20 mM potassium sulfate 18:82Fl ow ra te : 1.2D ete c to r : UV 254CHROMATOGRAMRetention t ime: 5Internal standard: p-hydroxyethyltheophyllineOTHER SUBSTANCESExtracted: metabolitesKEYWORDSplasmaREFERENCEKam ali, F.; Herd, B. Liquid-liquid extraction and an alysis of parace tamo l (acetam inophen) and its m ajorme tabolites in biological fluids by reversed-phase ion-pair chromatography. J.Chromatogr., 1990,530,222-225SAMPLEMatr ix : bu lkSample preparation: Prepare a 750 |xg/mL solution in 10 mM pH 2.5 orthophosphoricacid, sonicate for 10 min, filter (0.2 |xm), inject a 15 |xL aliquot.HPLCVARIABLESG ua rd co lum n: 4 X 4 5 jxm LiChrosphe r 100C ol um n: 125 X 4 3 |xm Spherisorb ODS-IM ob ile p h a s e : Gradient. A was wa ter containing 5 mL/L 85% orthophosphoric acid and0.56 mL/L hexylamine. B was MeCN.water 90:10 containing 5 mL/L 85% orthophos-phoric acid and 0.56 mL/L hexylamine. A:B from 91:9 to 86:14 over 4 min, maintain at86:14 for 13 min, to 55:45 over 11 min, maintain at 55:45 for 8 min, re-equilibrate atinitial conditions for 20 min.F low ra te : 0 .7In jec t ion vo lume : 15D ete c to r : UV 210C H R O M A T O G R A MRetention time: 5.7


9/26

OTHZR SUBSTANCESSimultaneous: acetylcodeine, benzocaine, caffeine, cocaine, codeine, diamorphine, lido-caine, 6-monoacetylmorphine, morphine, noscapine, papaverine, procaineREFERENCEGrogg-Sulser, K.; Helmlin, H.-J .; Clerc, J .-T. Qualitative and qua ntita tive dete rm inatio n of illicit heroinstreet samples by reversed-phase high-performance liquid chromatography: method development byCARTAGO-S. J.ChromatogrA, 1995, 692, 121-129SAMPLEMatrix: bulk, formulationsSa mple p rep ara ti on : Weigh out bulk drug, capsule contents, granules, or powders equiv-alent to 35 mg cephalexin, add 1 mL 2.52 mg/mL acetaminophen in MeOH-.water 20:80 ,make up to 50 mL with water, inject a 20 |xL aliquot.HPLCVARIABLESColumn: 300 X 3.9 10 [xm jxBondapak C18Mobile phase : MeOH: 1.25% acetic acid 25:75Flow rate: 1Injection volume: 20D etec tor: UV 254CHROMATOGRAMRetention t ime: 6Internal standard: acetaminophenOTHER SUBSTANCESSimultaneous: cephalexinKEYWORDScapsules; granules; powder; acetaminophen is ISREFERENCEHsu, M.C; Lin, Y-S.; Chung, H.-C. High-performance liquid chromatographic method for potency de-termination of cephalexin in commercial preparations and for stability studies. J.Chromatogr.A,

1995, 692, 6 7 - 7 2SAMPLEMatrix: dialysateSample p rep a ra ti on : Dialyze blood with Ringer's solution, inject a 0.5 uX aliquot of thedialysate.HPLCVARIABLESColumn: 14 X 1 3 fim BAS Sep-Stik ODS (Bioanalytical Systems)Mobile ph as e : 50 mM pH 5.0 ammonium acetate bufferFlow rate: 0.2Injection volume: 0.5Detec tor: UV 250CHROMATOGRAMRetention time: 0.5Limit of qu an tita tio n: 300 ng/mLOTHER SUBSTANCESExtracted: metabolites


10/26

KEYWORDSrat; microboreREFERENCEChen, A.; Lunte, CE. Microdialysis sampling coupled on-line to fast microbore liquid chromatography.J.Chromatogr.A, 1995, 691, 2 9 - 3 5SAMPLEMatrix: dialysateSample preparation: Inject an aliquot directly.HPLCVARIABLESColum n: 100 X 1 5 jxm ODS SepStik (Bioanalytical Systems)M obile phase : MeCN: 50 mM pH 2.5 ammonium phosphate buffer 7:93Flow rate: 0.1Injection volume: 7Detec tor: UV 250C H R O M A T O G R A MRetention time: 4.5Lim it of det ec tio n: 100 ng/mLOTHER SUBSTANCESExtracted: metabolitesKEYWORDSmicrobore; ratREFERENCESteele, K.M.; Lunte, CE. Microdialysis sampling coupled to on-line microbore liquid chromatographyfor pharmacokinetic studies. J.Pharm.Biomed.AnaL, 1995, 13, 149-154SAMPLEMatrix: formulationsSa mple p repa ra ti o n : Weigh out powdered sample containing 51 mg acetaminophen, add80 mL MeOH, sonicate for 10 min, dilute to 100 mL with MeOH, centrifuge. Remove a 5mL aliquot of the supernatan t and add it to 1 mL 2 mg/mL resorcinol, add 2 mL MeOH,make up to 20 mL with 50 mM pH 3.0 triethylam ine phosphate, inject an aliquot.HPLC VARIABLESColu mn: 150 X 3.2 5 |xm Hypersil ODSM obile p has e: TH F: 50 mM pH 3.0 triethylamine phosphate 12:88Flow rate: 0.6Injection volume: 20D etec tor: UV 275C H R O M A T O G R A MRetention t ime: 15In te rn al s ta nd ar d: resorcinol (9)OTHER SUBSTANCESSim ultaneous: aspirin (post-column irradiation gives an increase in peak height), caffeine,

propyphenazone


11/26

REFERENCEDi Pietra, A.M.; Gatti, R.; Andrisano, V.; Cavrini, V. Application of high-performance liquid chromatog-raphy with diode-array detection and on-line post-column photochemical derivatization to the deter-mination of analgesics. J.Chromatogr.A, 1996, 729, 3 5 5 - 3 6 1

SAMPLEMatrix: formulationsSample preparation: Finely powder half a tablet, add 9 mL mobile phase, sonicate for 20min, make up to 10 mL with mobile phase, filter (Whatman type 40 and 0.2 |xm Millipore),inject an aliquot of the filtrate.HPLC VARIABLESColumn: 250 X 4 5 ^m LiChrospher 100 CNMobile phase: MeCN:THF:buffer 7:6:87 (Buffer was 0.8% acetic acid containing 5 mMsodium hexanesulfonate, 10 mM di-n-butylamine, and 0.12% phosphoric acid, pH 3.3*)Flow rate: 1Injection volume: 20Detector: UV 310CHROMATOGRAMRetention time: 4.25Limit of detection: 1.9 |xg/mLOTHER SUBSTANCESSimultaneous: caffeine (UV 298), chlorpheniramine (UV 265), guaifenesin (glycerylguai-

colate) (UV 284), phenylpropanolamine (UV 260)KEYWORDStabletsREFERENCEIndrayanto, G.; Sunarto, A.; Adriani, Y. Simultaneous assay of phenylpropanolamine hydrochloride,caffeine, parac etam ol, glycerylguaiacolate and c hlorphe niram ine in Silabat ta blet usin g HPLC withdiode array detection. J.Pharm.Biomed.AnaL, 1995, 13, 1555-1559SAMPLEMatrix: formulationsSample preparation: 75 |xL Sample + 6 mL mobile phase, vortex for 2 min, add 300 JXL300 |xg/mL acetaminophen, make up to 10 mL with mobile phase, mix for 2 min, inject a5 |xL aliquot.HPLCVARIABLESColumn: 250 X 4.6 5 |xm Spheri-5 ODS (Applied Biosystems)Mobile phase: MeOH:buffer 30:70 (Buffer was 900 mL 50 mM Na2HPO4 + 18.75 mLtetrabutylammonium phosphate, pH adjusted to 6.S with 1 N phosphoric acid.)Flow rate: 1.2Injection volume: 5Detector: UV 254CHROMATOGRAMRetention time: 3.8Internal standard: acetaminophenOTHER SUBSTANCESSimultaneous: 5-aminosalicylic acid


12/26

KEYWORDSacetaminophen is IS; rectal suspension; enemaREFERENCEHenderson, L.M.; Johnson, CE.; Berardi, R.R. Stability of mesalamine in rectal suspension diluted withdistilled w ater. Am.J.Hosp.Pharm., 1994, 51, 2955-2957SAMPLEMatrix: formulationsSample preparation: Add one tablet to 10 mL MeOH and 80 mL dichloromethane, soni-cate for 5 min, dilute to 100 mL with dichloromethane, dilute a 2 mL aliquot to 25 mLwith mobile phase, inject a 10 |xL aliquot.HPLCVARIABLESGuard column: 20 X 4.6 5 |xm SupelcosilColumn: 33 X 4.6 3 |jim SupelcosilMobile phase: Dichloromethane:3.33% ammonium hydroxide in MeOH 98.5:1.5Flow rate: 2Injection vo lume: 10Detector: UV 244CHROMATOGRAMRetention time: 4Limit of detection: 100 ng/mLOTHER SUBSTANCESSimultaneous: propoxypheneNoninterfering: impurities, p-nitrophenol, p-hydroxyacetophenone, 4-aminophenolKEYWORDStablets; normal phaseREFERENCEAscah, T.L.; Hunter, B.T. Sim ultane ous high-performance liquid chromatog raphic de term inatio n of pro-

poxyphene and acetaminophen in pharmaceutical preparations. J.Chromatogr., 1988, 455, 279-289SAMPLEMatrix: formulationsSample preparation: Powder levodopa/carbidopa tablets or contents of capsules, weigh outan amount equivalent to about 100 ng levodopa, add 30 mL 0.1 M HCl, sonicate, makeup to 50 mL with 0.1 M HCl, mix, filter (0.45|xm), discard first 5 mL filtrate. 10 mLFiltra te + 50 mL 0.5 mg/mL acetaminophen in MeOH: mobile phase 75:175, make up to100 mL with mobile phase, mix, inject a 20 |xL aliquot.HPLCVARIABLESColumn: 300 X 3.9 10 jxm jxBondapak C18Mobile phase: 3% aqueous acetic acidFlow rate: 1.5Injection volume: 20Detector: UV 280CHROMATOGRAMRetention time: 9Internal standard: acetaminophen


13/26

OTHER SUBSTANCESSimul taneous: levodopa, carbidopaKEYWORDStablets; capsules; acetaminophen is ISREFERENCETing, S. Liquid chromatographic determination of levodopa and levodopa-carbidopa in solid dosageforms: collaborative study. J.Assoc.Off.Anal.Chem., 1987, 70, 987-990SAMPLEMatrix: formulationsH P L C V A R I A B L E SC o l u m n : 300 X 3 .9 ixBond apak C 18M o b i l e p h a s e : M eO H : buf fe r 20 :8 0 (Buffer was 15 m M 1-bu tanesu l fon ic ac id + 1 5 m MK H 2 P O 4 + 2 m L / L t r i e t h y l a m i n e , p H a d j u s t e d t o 4 .8 0 . 1 w i t h d i l u t e p h o s p h o r i c a ci d. )Colum n tem peratu re: 50Flow rate: 2Inject ion volum e: 20Detector: UV 214CHROMATOGRAMRetent ion t ime: 2.8OTHER SUBSTANCESSimul taneous: codeine, benzoic acid, p-aminophenol, codeine N-oxide, codeinoneKEYWORDSelixir; stability-indicatingREFERENCESisco, W.R.; Rittenho use, CT .; Ev erh art, L.A.; McL aughlin, A.M. Sim ultaneo us high-performance liquidchromatographic stability-indicating analysis of acetaminophen, codeine phosphate, and sodium ben-

zoate in elixirs. J.Chromatogr., 1986, 354, 355-366SAMPLEMatrix: formulationsSample preparat ion: Dissolve capsules an d tab lets in MeOH :pH 4.0 w ater 1:1, sh ake for1 (capsules) or 4 (tablets) h, dilute a 10 mL aliquot with 40 mL pH 3.2 water, filter (0.45ixm), collect last portion of filtrate, inject a 20 jxL aliquot. (pH 3.2 and 4.0 water areprepared by adjusting pH of distilled water with phosphoric acid.)HPLC VARIABLESColumn: 300 X 3.9 ixBondapak C18Mobile phase: M eO H: buffer 7:9 3 (Buffer w as 15 mM K H2PO 4 + 2 mL triethylamine perliter. Adjusted to pH 2.35 0 . 1 w ith concentrated pho sphoric acid.)Column tem peratu re: 40Flow rate: 3Injec tion volum e: 20Detector: UV 214CHROMATOGRAMRetent ion t ime: 2 .7


14/26

OTHER SUBSTANCESSimul taneous: codeine, p-aminophenol, codeine-N-oxide, codeinone, degradation productsKEYWORDScapsules; tablets; ruggedREFERENCESisco, W.R.; Rittenhouse, CT.; Everhart, L.A. Simultaneous high-performance liquid chromatographicstability-indicating analysis of acetaminophen and codeine phosphate in tablets and capsules.J.Chromatogr., 1985, 348, 2 5 3 - 2 6 3SAMPLEMatrix: formulationsSample preparat ion: Pulverize tablets and weigh out 1 g, add 1 mL formic acid, add 25m l MeOH, shak e mechanically for 10 min, m ake up to 50 mL with m ethan ol. Remove

10 mL and centrifuge. 5 mL Supernatant + 5 mL 0.0025% p-hydroxybenzoic acid inM eOH : w ater 2 0:80 , mak e up to 25 mL with w ater, inject an aliquot. (Analyze within 1h.)HPLC VARIABLESColumn: 250 X 4.6 LiChrosorb RP8Mobile phase: MeO H: 200 mM pH 3.5 ph osph ate buffer .water 20 :10:7 0Flow rate: 1Inject ion volum e: 10Detector: UV 254CHROMATOGRAMRetention time: 8.5Internal s tandard: p-hydroxybenzoic acid (18)OTHER SUBSTANCESSimul taneous: asp irin, p-am inoph enol, 3-O-acetylascorbic acid, 2-O-acetylascorbic acid, Vi-tamin C, saccharin, O-acetyl-p-aminophenol, salicylic acid (UV 280), diacetyl-p-amino-phenol (UV 280)KEYWORDStabletsREFERENCEThomis, R.; Roets, E.; Hoogmartens, J. Analysis of tablets containing aspirin, acetaminophen, and as-corbic acid by high-performance liquid chrom atography. J.Pharm.Sci., 1984, 73, 1830-1833SAMPLEMatrix: formulationsSample preparat ion: Dilute with water, filter (0.45 |xm), inject a 20 |JLL aliquot.HPLCVARIABLESColumn: 300 X 4 jxBondapak C18Mobile phase: M eOH : w ate r: glacial acetic acid 45 :5 5: 2 containing 5 mM octanesulfonicacidFlow rate: 2.5Inject ion volume: 20Detector: UV 280CHROMATOGRAMRetention time: 1.5


15/26

OTHER SUBSTANCESSimul taneous: guaifenesin, pseudoephedrine, pholcodine, methyl paraben, ethyl paraben,propyl paraben, butyl parabenKEYWORDScough mixtureREFERENCECarnevale, L. Simultaneous determination of acetaminophen, guaifenesin, pseudoephedrine, pholcodine,and paraben preservatives in cough mixture by high-performance liquid chromatography.J.Pharm.ScL, 1983, 72, 196-198SAMPLEMatrix: formulationsSample preparat ion: Add 1 tabl et to 95 mL w ater, place on a stea m ba th for 15 min, cool,

mix for 15 min, sonicate, allow to stand, filter, inject a 13 |xL aliquot.HPLCVARIABLESColumn: jxBondapak C18Mobile phase: M eO H: buffer 25 :7 5 (Buffer w as 0.01 N KH 2PO 4 + 5OmM KNO3, adjustedto pH 4.5 with 3 N phosphoric acid.)F low rate : 1.1Inject ion volum e: 13Detector: UV 283CHROMATOGRAMRetent ion t ime: 5.9OTHER SUBSTANCESSimul taneous: hydrocodone, p-aminopheno l, hydrom orphone, codeine, p -chloroacetanilideKEYWORDStablets; stability-indicatingREFERENCEWallo, W.E.; D'Adamo, A. Simultaneous assay of hydrocodone bitartrate and acetaminophen in a tabletformulation. J.Pharm.ScL, 1982, 71, 1115-1118

SAMPLEMatrix: formulationsSample preparat ion: 3 mL Sample + 5 mL 200 mg/mL o-dinitrobenzene in 1:1 MeOH:water, dilu te to 50 mL w ith 1:1 M eO H: wa ter, inject a 15 |xL aliquo t.HPLCVARIABLESColumn: 300 X 4 ixBondapak C18Mobile phase: MeOH:water:ammonium formate buffer 45:54:1 (Prepare ammonium for-m ate buffer by diluting 34 mL 28-30% amm onia w ith 30 mL water, add 30 mL 98% formicacid (C aution! Exotherm ic!). W hen cool dilu te th is m ixtu re (pH 3.9) to 100 mL with water.)Flow rate: 2Inject ion volum e: 15Detector: UV 280CHROMATOGRAMRetent ion t ime: 4Internal s tandard: o-dinitrobenzene (11)


16/26

OTHER SUBSTANCESSimultaneous: guaifenesin, dextromethorphan, p-aminophenolKEYWORDScough syrupREFERENCEMcSharry, W.O.; Savage, I.V.E. Simultaneous high-pressure liquid chromatographic determination ofacetaminophen, guaifenesin, and dextromethorphan hydrobromide in cough syrup. J.Pharm.ScL,1980, 69, 212-214SAMPLEMatrix: microsomal incubationsSam ple p repa ra ti on : 250 |xL Microsomal incubation + 1 mL ice-cold ethyl acetate + 100|JLL 50 mM lip-hydroxytestosterone, mix, add 1.5 mL ethyl acetate, vortex, centrifuge.

Remove the organic layer and evaporate it to dryness under a stream of nitrogen, recon-stitute the residue in 150 u,L MeOH-.water 20:80, inject an aliquot.HPLCVARIABLESGuard column: 5 |xm Supelco LC-18Colu mn: 150 X 4.6 5 um Supelco LC-18M obile phase: Gradient. A was MeOH: water 30:70 adjusted to pH 4.5 with glacial aceticacid. B was MeCN:MeOH 10:90 adjusted to pH 4.5 with glacial acetic acid. A:B 87:13for 34 min, to 50:50 over 10 min, re turn to initial conditions over 5 min.Flow ra te : 1.3D etec tor: UV 240C H R O M A T O G R A MRetention time: 1.8Internal standard: lip-hydroxytestosterone (26)OTHER SUBSTANCESExtracted: 6p-hydroxytestosteroneREFERENCEChiba, M.; Nishime, J.A.; Lin, J.H. Potent and selective inactivation of human liver microsomal cyto-chrome P-450 isoforms by L-754,394, an investigational human immune deficiency virus proteaseinhibitor. J.Pharmacol.Exp.Ther., 1995, 275, 1527-1534SAMPLEMatrix: solutionsHPLCVARIABLESColu mn: 250 X 4.6 8 jxm Unisphere-PBD (polybutadiene on alumina) (Biotage, Charlottes-ville, VA)Mobile phas e: MeCN: water 20:80Flow rate: 1D etec tor: UV 254C H R O M A T O G R A MRetent ion t ime: 3OTHER SUBSTANCESSimultaneous: aspirin, phenacetin, salicylamide


17/26

REFERENCEJ edrejew ski, RT.; Taylor, L.T. Comparison of silica-, alum ina-, an d polymer-based statio nar y ph ases forreversed-phase liquid chromatography. J.Chromatogr.Sci., 1995, 33, 4 3 8 - 4 4 5

SAMPLEMatrix: solutionsHPLCVARIABLESColumn: 250 X 4.6 5 |xm S upelcosil LC-DP (A) or 250 X 4 5 |xm L iCh rosp her 100 RP-8 (B)Mobile phase: MeCN:0.025% phosphoric acid:buffer 25:10:5 (A) or 60:25:15 (B) (Bufferwas 9 mL concentrated phospho ric acid and 10 mL triethy lam ine in 900 mL water, adjustpH to 3.4 with dilute phosphoric acid, make up to 1 L.)Flow rate: 0 .6Inject ion vo lume: 25Detector: UV 229CHROMATOGRAMRetention time: 4.75 (A), 3.68 (B)OTHER SUBSTANCESAlso analyzed: acebutolol, acepromazine, acetazolamide, acetophenazine, albuterol, alpra-zolam, amitriptyline, amobarbital, amoxapine, antipyrine, atenolol, atropine, azatadine,baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bupivacaine, buspi-

rone, bu tab arb ital, bu talbita l, caffeine, carbam azepine, cetirizine, chloreyelizine, chlordi-azepoxide, chlormezanone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropam-ide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine,clonazepam, clonidine, clozapine, cocaine, codeine, colchicine, cyclizine, cyclobenzaprine,dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem, diphenhydramine,diphenidol, diphenoxylate, dipyridamole, disopyramide, dobutamine, doxapram, doxepin,droperidol, encainide, ethidium bromide, ethopropazine, fenoprofen, fentanyl, flavoxate,fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvoxamine, furosemide, glutethimide,glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hy-drocodone, hydrom orphone, hydroxy chloroquine, hydroxyzine, ibuprofen, imip ram ine, in-domethacin, ketoconazole, ketoprofen, ketorolac, labetalol, levorphanol, lidocaine, lora-tadine, lorazepam, lovastatin, loxapine, mazindol, mefenamic acid, meperidine,mephenytoin, mepivacaine, mesoridazine, metaproterenol, methadone, methdilazine,methocarbamol, methotrexate, methotrimeprazine, methoxamine, methyldopa, methyl-phenidate, metoclopramide, metolazone, metoprolol, metronidazole, midazolam, moclo-bemide, morphine, nadolol, nalbuphine, naloxone, naphazoline, naproxen, nifedipine, ni-zatidine, norepinephrine, nortriptyline, oxazepam, oxycodone, oxymetazoline, paroxetine,pemoline, pentazocine, pentobarbital, pentoxifylline, perphenazine, pheniramine, pheno-barbital, phenol, phenolphthalein, phentolamine, phenylbutazone, phenyltoloxamine,phenytoin, pimozide, pindolol, piroxicam, pramoxine, prazepam, prazosin, probenecid,procainamide, procaine, prochlorperazine, procyclidine, promazine, promethazine, pro-pafenone, propantheline, propiomazine, propofol, propranolol, protriptyline, quazepam,quinidine, quinine, racemethorphan, ranitidine, remoxipride, risperidone, salicylic acid,scopolamine, secobarbital, sertraline, sotalol, spironolactone, sulfinpyrazone, sulindac,temazepam, terb utaline, terfenadine, tetracaine , theophylline, thiethylperazine, thiopen-tal , thioridazine, thiothixene, timolol, tocainide, tolbutamide, tolmetin, trazodone, triam-terene, triazolam, trifluoperazine, triflupromazine, trimeprazine, trimethoprim, trimipra-mine, verap am il, warfarin, xylometazoline, yohimbine, zopiclone

KEYWORDSalso details of plasma extraction


18/26

REFERENCEKoves, E.M. Use of high-performance liquid chromatography-diode array detection in forensic toxicology.J.Chromatogr.A, 1995, 692, 103-119SAMPLEMatrix: solutionsSample preparation: Inject a 2 (xL aliquot.HPLCVARIABLESColumn: 30 X 4.6 3 |xm Hypersil ODSMobile phase: MeOH: 50 mM pH 6.2 phosphate buffer 15:85Flow rate: 2Injection volume: 2Detector: UV 280REFERENCEShah , K.R; Chang, M.; Riley, CM . Autom ated analytica l system s for drug development stu dies . 3. MuI-tivessel dissolution testing system based on microdialysis sampling. J.Pharm.Biomed.AnaL, 1995,13, 1235-1241SAMPLEMatrix: solutionsSample preparation: Prepare a 0.5 mg/mL solution in water, inject a 5 pX. aliquot.HPLCVARIABLESColumn: 250 X 4.6 Zorbax RXMobile phase: Gradient. A was 150 mM phosphoric acid and 50 mM triethylam ine. B wasMeCN-.water 80:20 containing 150 mM phosphoric acid and 50 mM triethylamine. A:B100:0 for 2.2 min then to 0:100 over 30 min.Column temperature: 30Flow rate: 2Injection volume: 5Detector: UV 210CHROMATOGRAMRetention time: 8.3OTHER SUBSTANCESSimultaneous: aprobarbital, butabarbital, chlordiazepoxide, chloroxylenol, chlorproma-zine, clenbuterol, cortisone, danazol, diflunisal, doxapram, estrone,fluoxymesterone,me-fenamic acid, methyltestosterone, nicotine, oxazepam, phentermine, phenylpropanolam-ine, progesterone, sulfamethazine, sulfanilamide, testosterone, testosterone propionate,tranylcypromine, tripelennamineInterfering: N-acetylprocainamideKEYWORDSdetails for purification of triethylamine in paperREFERENCEHill, D.W.; Kind, A.J. The effects of type B silica and triethylamine on the retention of drugs in silicabased reverse phase high performance chromatography. J.Liq.Chromatogr., 1993, 16, 3941-3964SAMPLEMatrix: solutionsSample preparation: Dissolve compounds in MeCN: water 80:20, inject a 1 |xL aliquot.


19/26

HPLCVARIABLESColumn: 150 X 1 3 ^m Hitachi-Gel 3057 ODS silica (Hitachi)Mobile phase: MeCN: water 25:75Flow rate: 0 .03Inject ion volume: 1Detector: UV 254CHROMATOGRAMRetention time: 8OTHER SUBSTANCESSimul taneous: caffeine, dipyrone (sulpyrin), guaifenesin (guaiacol glycerol ether), bucetin(3-hydroxy-p-butyrophenetidine), methyl p-hydroxybenzoate, phenacetinKEYWORDSsemi-microREFERENCEMatsushima, Y; Nagata, Y; Niyomura, M.; Takakusagi, K.; Takai, N. Analysis of antipyretics by sem-imicro liquid chromatography. J.Chromatogr., 1985, 332, 2 6 9 - 2 7 3SAMPLEMatrix: solutionsSample preparat ion: Dissolve compounds in MeOH, inject a 1 |xL aliquot.HPLCVARIABLESColumn: 150 X 1 3 |xm H itachi-Gel 3&L1 poro us polym er (Hitachi)Mobile phase: MeOH : ammonia 99 :1Flow ra te : 0.03Inject ion volum e: 1Detector: UV 254CHROMATOGRAMRetention time: 3.26OTHER SUBSTANCESAlso analyzed : caffeine, dipyrone (sulpyrin), bucetin (3-hydroxy-p-butyrophenetidine), phe-nacetin, mefenamic acid, aspirin, salicylamide, salicylic acid, ethenzamide (o-ethoxyben-zamide), theobromine, theophyllineKEYWORDSsemi-microREFERENCEMatsushima, Y; Nagata, Y; Niyomura, M.; Takakusagi, K.; Takai, N. Analysis of antipyretics by sem-

imicro liquid chrom atography. J.Chromatogr., 1985, 332, 2 6 9 - 2 7 3SAMPLEMatrix: urineSample preparat ion: Dilute urine with water, filter (0.45 |xm), inject a 20 |xL aliquot ofthe filtrate.HPLCVARIABLESGuard co lumn: 5 |xm Resolve C18 Gu ard-P ak (Waters)Column: 100 X 8 5 |xm Resolve C18 Radial Compression Module (Waters)


20/26

M obile ph as e: MeOH: 100 mM KH2PO 4: glacial acetic acid 4:95 :1Flow rate: 2.5Injection volume: 20D etec tor: UV 248C H R O M A T O G R A MRetent ion t ime: 4.47Lim it of det ect ion : 2 ng/mLOTHER SUBSTANCESExtracted: metabolites, acetaminophen glucuronide, acetaminophen sulfateKEYWORDSpharmacokineticsREFERENCEGoicoechea, A.G.; Lopez de Alda, M.J .; Vila-Jato, J .L. A validated high-performance liquid chromato-graphic method for the determination of paracetamol and its major metabolites in urine.J.Liq.Chromatogr., 1995, 18, 3257-3268SAMPLEMatrix: urineSample p re pa ra tio n : 0.3 mL Urine + 1 mL 100 mM pH 4.5 acetate buffer containing 20mg/mL sodium pyrosulfite + 20 mg Limpet Acetone Powder. Incubate 3 h 37, add 100|xL 400 mg/L phenacetin, extract twice w ith 4 mL of e ther : dichloromethane: isopropanol

60:40:1. Add 0.5 mL pH 6.5 50 mM phosphate buffer containing 20 mg/mL sodium py-rosulfite, shake, allow phases to separate, evaporate upper organic layer under a streamof nitrogen and inject aqueous layer.HPLCVARIABLESColu mn: 100 X 4.6 Chrompack microsphere C18M obile phase : Gradient. A was 50 mM pH 6.6 phosphate buffer. B was MeCN: 50 mM pH6.5 phosphate buffer 25:75. A:B from 90:10 to 10:90 over 50 min, maintain at 10:90 for2 min.Flow rate: 1.2Injection volume: 250Detector: UV 254CHROMATOGRAMInternal standard: phenacetinOTHER SUBSTANCESSimultaneous: metabolitesKEYWORDSPigREFERENCEMonshouwer, M.; Witkamp, R.F.; Pijpers, A.; Verheijden, J.H.M.; Van Miert, A.S.J.P.A.M. Dose-depen-dent pharmacokinetic interaction between antipyrine and paracetamol in vivo and in vitro whenadministered as cocktail in pig. Xenobiotica, 1994, 24, 3 4 7 - 3 5 5SAMPLEMatrix: urine


21/26

Sample preparat ion: 1 mL U rine + 4 mL 2 M pH 5.0 a cetate buffer (+ 50 |JLL p-gluco-ronidase-sulfatase at 37 overnight if required to hydrolyze conjugates). Centrifuge 200IxL aliquots for 5 min, inject a 10-20 jxL aliquot.HPLCVARIABLESColumn: 300 X 4.6 10 |xm ixBondapak C18Mobile phase: MeOH :HOAc: 100 mM KH 2PO 4 7:0.75:92.25Flow rate: 2Inject ion volume: 10-20Detector: UV 248; E, Bioanalytical Systems LC-4, TL-3 glassy carbon electrode + 0.60 V,Ag/AgCl reference electrode, output 10-50 nA/VCHROMATOGRAMRetent ion t ime: 8Limit of detect ion: 70 ng/mL (UV), 15 ng/mL (E)OTHER SUBSTANCESExtracted: metabolitesREFERENCEWilson, J .M.; Slattery, J .T.; Forte, A.J.; Nelson, S.D. Analysis of acetamino phen me tabolites in uri ne byhigh-performance liquid chromatography with UV and amperometric detection. J.Chromatogr., 1982,227, 453-462 ANNOTATED BIBLIOGRAPHYVisentini, J .; Kwong, E. C ; C arrier, A.; Zidarov, D.; Be rtran d, M .J. C omparison of softwares use d for th edetection of analytes present at low levels in liquid chromatographic-mass spectrometric experi-ments . J.Chromatogr.A, 1995, 712, 31-43 [LC-MS]Akhtar, M.J.; Khan, S.; Hafiz, M. High-performance liquid chromatographic assay for the determinationof paracetamol, pseudoephedrine hydrochloride and triprolidine hydrochloride. J.Pharm.Biomed.AnaL, 1994, 12, 379-382 [simultaneous pseudoephedrine, triprolidine; formulations]Bogusz, M.; Erkens, M. Reversed-phase high-performance liquid chromatographic database of retentionindices and UV spectra of toxicologically relevant substances and its interlaboratory use.J.Chromatogr.A, 1994, 674, 97-126 [gradient; also acebutolol, acecarbromal, acepromazine, aceta-zolamide, allobarbital, allopurinol, alprazolam, alprenolol, amiloride, amiodarone, amitriptyline,amobarbital, amoxapine, amp hetam ine, aprob arbital, vitamin C, aspirin, atenolol, atrazine, atropine,barbital, benzocaine, benztropine, betaxolol, bisacodyl, brallobarbital, bromazepam, bromphenira-mine, bupivacaine, bupranolol, buprenorphine, buspirone, butalbital, butaperazine, butobarbital, caf-feine, carbam azepine , ca rbaryl, carbrom al, chlordiazepoxide, chlormeza none, chloroquine, chlorprom-azine, chlorprothixene, chlorthalidone, c imetidine, cinchocaine, clobazam, clomipram ine, clonazepam,clonidine, clopamide, clopenthixol, clorazepate, clozapine, cocaine, codeine, colchicine, coumarin, cy-clobarbital, cyclopentobarbital, demoxepam, desipramine, dextromethorphan, dextromoramide, dex-tropropoxyphene, diamorphine, diazepam, diazoxide, diclofenac, digoxin, diltiazem, dimenhydrinate,diphenhydramine, dipyridamole, disopyramide, dothiepin, doxepin, doxylamine, droperidol, ephed-rine, estazolam, ethacrynic acid, ethosuximide, fenfluramine, fenoprofen, fentanyl, flecainide, flu-

mazenil, flunarizine, flunitrazepam, fluoxetine, flupenthixol, flurazepam, fluvoxamine, furosemide,glyburide, glipizide, glutethimide, guaifenesin, haloperidol, hydrochlorothiazide, hydrocodone, hy-dromorphone, hydroxyzine, ibuprofen, imipramine, indomethacin, isoniazid, isosorbidedinitrate,ketam ine, labetalol, m etho trim epra zine, levorphanol, lidocaine, loprazolam, lorazepam, loxapine, ma-trotiline, meclozine, medazepam, mephenytoin, mepivacaine, metapramine, methadone, metham-phetamine, methaqualone, methohexital, methylphenidate, metipranolol, metoclopramide, metopro-lol, metronidazole, midazolam, monolinuron, morazone, morphine, nadolol, nalorphine, naloxone,naproxene, nicotinamide, nicotine, niflumic acid, nikethamide, nimodipine, nitrazepam, nitrendipine,nitrofurantoin, nitroglycerine, noscapine, orciprenaline, orphenadrine, oxazepam, oxazolam, oxpren-olol, oxycodone, oxyphen butazone, pap ave rine , pemoline, pentazocine, pe ntob arbital, pentoxifylline,perazine, perphenazine, meperidine, phenacemide, phenacetin, phenazone, phcencyclidine, phenel-


22/26

zine, pheniram ine, ph enobarbital, p hente rmin e, phen ylbutazone, phenytoin, pindolol, piroxicam, pra-zepam, primidone, probenecid, procainamide, procaine, prochlorperazine, promazine, promethazine,propafenone, propoxur, propranolol, propyphenazone, protriptyline, quinidine, quinine, ranitidine,reserpine, saccharin, salicylamide, salicylic acid, scopolamine, secobarbital, sotalol, spironolactone,strychnine, sulphadiazine, sulpiride, suprofen, temaz epam , terfenadine, tetraca ine, tetrazepam , the-baine, theobromine, theophylline, thiabendazole, thiopental, thioridazine, tiaprofenic acid, timolol,tocainide, tolbutamide, trancylpromine, trazodone, triamterene, triazolam, trichlormethiazide, tri-fluoperazine, trifluperidol, triflupromazine, trimethoprim, trimipramine, tripelenamine, tripolidine,verapamil, vinylbarbital, warfarin, yohimbine, zolpidem]

Gurley, B.J.; Zermatten, S.; Skelton, D. Determination of antipyrine in human serum by direct injectionrestricted access media liquid chromatography. J.Pharm.Biomed.AnaL, 1994, 12, 1591-1595 [ex-tracted antipyrine; serum; column temp 37; acetaminophen is IS]Hill, D.W.; Kind, A. J . Re versed-phase solvent gradie nt H PLC rete ntion indexes of drug s. J.Anal.ToxicoL,1994,18, 23 3-2 42 [also acepromazine, acetophenazine, albuterol, aminophylline, amitriptyline, amo-barbital, am oxapine, am phetam ine, am ylocaine, antipyrine, aprobarbital, aspirin, atenolol, atropine,avermectin, barbital, bebrisoquine, benzocaine, benzoic acid, benzotropine, benzphetamine, berber-

ine, bibucaine, bromazepan, brompheniramine, buprenorphine, buspirone, butabarbital, butacaine,butethal, caffeine, carbamazepine, carbromal, chloamphenicol, chlordiazepoxide, chloroquine, chlo-rothiazide, chloroxylenol, chlorphenesin, chlorpheniramine, chlorpromazine, chlorpropamide, chlor-tetracycline, cimetidine, cinchonidine, cinchonine, clenbuterol, clonazepam , clonixin, clorazepate, co-caine, codeine, colchicine, cortisone, coumarin, cyclazocine, cyclobenzaprine, cyclothiazide,cyheptamide, cymarin, danazol, danthron, dapsone, desipramine, dexamethasone, dextromethor-phan, dextropropoxyphene, diamorphine, diazepam, diclofenac, diethylpropion, diethylstilbestrol, di-flunisal, digitoxin, digoxin, diltiazem, diphenhydramine, diphenoxylate, diprenorphine, dipyrone, di-sulfiram, dopamine, doxapram, doxepin, dronabinol, ephedine, epinephrine, epinine, estradiol,estriol, estrone, ethacrynic acid, ethosuximide, etonitazene, etorphine, eugenol, famotidine, fenben-dazole, fencamfamine, fenoprofen, fenproporex, fentanyl, flubendazole, flufenamic acid, flunitraze-pam, 5-fluorouracil, fluoxymesterone, fluphenazine, furosemide, gentisic acid, gitoxigenin, glipizide,glunixin, glutethimide, glybenclamide, guaiacol, halazepam, haloperidol, hydrochlorothiazide, hydro-codone, hydrocortisone, hydrom orphone, hydroxyquinoline, ibogaine, ibuprofen, iminostilbene, imip-ram ine, indom ethacin, isocarbostyril, isocarboxazid, isoniazid, isoproterenol, isoxsuprine, iverm ectin,ketamine, ketoprofen, kynurenic acid, levorphanol, lidocaine, lorazepam, lormetazepam, loxapine,mazindol, mebendazole, meclizine, meclofenamic acid, medazepam, mefenamic acid, megestrol, me-pacrine, meperidine, mephentermine, mephenytoin, mephesin, mephobarbital, mepivacaine, mesca-line, mesoridazine, methadone, methamphetamine, methapyrilene, methaqualone, methazolamide,methocarbamol, methoxamine, methsuximide, methyl salicylate, methyldopa, methyldopamine,methylphenidate, methylprednisolone, methyltestosterone, methyprylon, metoprolol, mibolerone,morphine, nadolol, nalorphine, naloxone, naltrexone, naphazoline, naproxen, nefopam, niacinamide,nicotine, nicotinic acid, nifedipine, niflumic acid, nitrazepam, norepinephrine, nortriptyline, nosca-pine, nylidrin, oxazepam, oxycodone, oxymorphone, oxyphenbutazone, oxytetracycline, papaverine,pargyline, pemoline, pentazocine, pentobarbital, persan tine, phenacetin, phenazocine, phenazopyri-dine, phencyclidine, phendim etrazine, phenelzine, pheniram ine, phenobarbital]

Ismail, S.; Kokwaro, G.O.; Back, D .J.; E dw ards, G. Effect of mala ria infection on the pharm acok ineticsof paracetamol in rat. Xenobiotica, 1994, 24, 527-533 [pharmacokinetics; rat; plasma; urine; ex-tracted metabolites; 3-acetamidophenol is IS]Konishi, H.; Yamaji, A. Measurement of theophylline metabolites produced by reaction with hepaticmicrosome by high performance liquid chromatography following solid phase extraction. Bio-

med.Chromatogr., 1994, 8, 189-192 [extracted theophylline; microsomal incubations; SPE; aceta-minophen is IS; mouse]Lau, G.S.N.; Critchley, J.A.J.H. The estimation of paracetamol and its major metabolites in both plasmaand urine by a single high-performance liquid chromatography assay. J.Pharm.Biomed.AnaL, 1994,12 , 1563-1572 [extracted metabolites; plasma; urine; blood; LOD 1 ng]Nivaud -Guerne t, E .; Guernet, M.; Ivanovic, D.; Medenica, M. Effect of eluent p H on the ionic and m o-lecular forms of the non-steroidal anti-inflammatory agents in reversed-phase high-performance liq-uid chromatography. J.Liq.Chromatogr., 1994, 17, 2343-2357 [also aspirin, flufenamic acid, keta-zone, mefenamic acid, niflumic, niflumic acid, nixylic acid, oxyphenbutazone, phenacetin,salicylamide, salicylic acid, sulfinpyrazone]


23/26

Oguro, T.; Gregus, Z.; M adhu, C ; L iu, L.; Klaa ssen, C D . Molybdate depletes hepatic 3-phosphoadenosine5-phosphosulfate and impairs the sulfation of acetaminophen in rats. J.Pharmacol.Exp. Ther., 1994,270, 1145-1151 [rat, extracted metabolites; serum; urine; bile]Shah, K.P.; Chang, M.; Riley, CM. Automated analytical systems for drug development studies. H-Asystem for dissolution testing. J.Pharm.BiomedAnal, 1994, 12, 1519-1527 [dissolution testing; for-mulations; tablets; also sulfamethoxazole, trimethoprim]Thom as, B.R.; Fang, X.G.; Shen, P.; Ghodb ane, S. Mixed ion pair liquid chro ma tography method for th esimultaneous assay of ascorbic acid, caffeine, chlorpheniramine maleate, dextromethorphan HBrmonohydrate and paracetamol in Frenadol sachets. J.Pharm.Biomed.Anal., 1994, 12, 85-90 [s imul-taneous caffeine, chlorpheniramine, dextromethorphan, vitamin C; formulations]van der Veen, J.; Eissens, A.C; Lerk, CF. Controlled release of paracetamol from amylodextrintablets: In vitro and in vivo results. Pharm.Res., 1994, 11, 384-387 [plasma; pharmacokinetics]Abounassif, M.A.; Abdel-Moety, E.M.; Gad-Kariem, R.A. HPLC-quantification of diethylamine salicylateand m ethyl nicotinate in ointments. J.Liq.Chromatogr., 1992,15, 625-636 [formulations; ointments;simultabeous diethylamine salicylate, methyl nicotinate; acetaminophen is IS; simultaneo us m ethylparaben, propyl parabenBa nnw arth , B.; Netter, P.; Lapicque, R ; G illet, P.; Pere, P.; Boccard, E.; Royer, R.J.; G aucher, A. Plasm aand cerebrospinal fluid concentrations of paracetamol after a single intravenous dose of propaceta-mol. Br.J.Clin.Pharmacol, 1992, 34, 79-81 [plasma; CSF; LOD 2 ng/mL]Curtis, M.A.; Pullen, R.H.; McKenna, K. HPLC determination of analgesics in human plasma and serumby direct injection on 80 Angstrom pore methyl bonded phase silica columns. J.Liq.Chromatogr.,1991, 14, 165-178 [plasma; serum; extracted salicylic acid]Aloba, O.T.; Adusumilli, P.S.; Nigalaye, A.G. High performance liquid chromatographic analysis of amulticomponent product using a silica stationary phase and an aqueous-organic mobile phase.J.Pharm.Biomed.Anal., 1991, 9, 335-340 [simultaneous butalbital, caffeine]Hays, P.A.; Lurie, LS. Quantitative analysis of adulterants in illicit heroin samples via reversed phaseH P L C J.Liq.Chromatogr., 1991, 14, 3513-3517 [also acetylcodeine, acetylmorphine, aspirin, ben-zocaine, caffeine, chloroquine, diamorphine, diazepam, diphenhydramine, dipyrone, lidocaine, meth-aqualone, monoacetylmorphine, morphine, nicotinamide, noscapine, papaverine, phenacetin, pheno-barbital, phenolphthalein, N-phenyl-2-naphthylamine, salicylic acid, strychnine]McCormick, C P ; S hihabi, Z.K. HPLC of fluorescent products of acetam inophen reaction w ith peroxi-dase. J.Liq.Chromatogr, 1990, 13, 1159-1171 [fluorescence detection; UV detection; simultaneousdegradation products]Molokhia, A.M.; Niazy, E.M.; El-Hoofy, S.A.; El-Dardari, M.E. Improved liquid chromatographic methodfor acyclovir determination in plasma. J.Liq.Chromatogr, 1990, 13, 981-989 [extracted acyclovir;plasma; acetaminophen is IS]Brinkman, U.A.T.; Frei, R.W.; Lingeman, H. Post-column reactors for sensitive and selective detectionin high-performance liquid chromatography: Categorization and applications. J. Chromatogr.,1989,492, 251-298 [post-column reaction; review]Siegers, CP .; Moller-Hartmann, W. Cholestyramine as an antidote a gainst paracetamol-induced hepato-and nephrotoxicity in the rat. Toxicol.Lett., 1989, 47, 179-184 [rat; urine; extracted metabolites]Lam, S.; Malikin, G. An improved micro-scale protein precipitation procedure for HPLC assay of ther-apeutic drugs in serum. J.Liq.Chromatogr, 1989, 12, 1851-1872 [serum; also amiodarone, aspirin,caffeine, chloramphenicol, flecainide, pentobarbital, procainamide, pyrimethamine, quinidine, the-ophylline, tocainide, trazodone; fluorescence detection; UV detection]Alvi, S.U.; Castro, F. A stability-indicating simultaneous analysis of acetaminophen and hydrocodonebitartrate in tablets formulation by HPLC J.Liq.Chromatogr., 1987, 10, 3413-3426 [stability-indi-cating; simultaneous codeine, hydrocodone; hydromorphone; tablets; column temp 30]Kinney, C D .; Kelly, J .G. Liquid chromatog raphic d eterm inatio n of parace tam ol and dextropropoxyphenein plasma. J.Chromatogr, 1987, 419, 433-437 [plasma; salicylamide is IS; LOD 100 ng/mL;pharmacokinetics]Fatmi, A.A.; Williams, G.V. Simultaneous determination of acetaminophen and hydrocodone bitartratein solid dosage forms by H P L C J.Liq.Chromatogr, 1987,10, 2461-2472 [simultaneoushydrocodone;formulations]Hill, D.W> Langner, K .J. HPLC photodiode a rray UV detection for toxicological dru g a nalys is.

J.Liq.Chromatogr, 1987, 10, 377-409 [also acepromazine, acetophenazine, acetophenetidine, ace-


24/26

tylprocainamide, aflatoxins, allylcyclopentenylbarbituric acide, allylisobarbituric acid, alphaprodine,alphenal, aminoantipyrine, aminobenzamide, aminobenzoate, aminobenzoic, aminobenzoic acid, ami-nophylline, amitriptyline, amobarbital, amylocaine, anisic acid, anthranilamide, antipyrine, apro-barbital, aspirin, atropine, barbital, benzoate, benzocaine, benzoic, benzoic acid, benzoylecgonine,benzphetamine, brucine, butabarbital, butacaine, butethal, butyl paraben, caffeine, cannabichro-mene, cannabinol, carbostyril, carvacrole, chloramphenicol, chlordiazepoxide, chloroethyltheophyl-line, chlorophenol, chloroquine, chlorotheophylline, chlorothiazide, chlorphenesin, chlorph eniram ine,chlorpromazine, chlorpropamide, cinchonidine, cinchonine, clonazepam, cocaine, codeine, colchicine,cortisone, coumarin, creatinine, cyclothiazide, cyheptamide, danazol, danthron, dapsone, DES, des-propanylfentanyl, dexamethasone, diallylbarbituric acid, diazepam, dibucaine, dichlorophene, di-drate, diethylstilbestrol, diethyltryptamine, dihydroxyphenethyl alcohol, dihydroxyphenylacetic acid,dihydroxyphenylglycol, dimethylbarbituric acid, diphenhydramine, diphenoxylate, diphenylhydan-toin, dipropyltryptamine, dithiodinicotinic acid, doxapram, dronabinol, dyphylline, estradiol, estriol,estrone, ethonitazene, ethosuximide, ethylmorphine, ethylnornicotine, ethylphenylmalonamide,ethyltolylmalonamide, etonitazene, eugenol, fenfluramine, fenoprofen, fentanyl, 5-fluorouracil, fluox-ym esterone, flurazepam, furosemide, gentisic, gentisic acid, gitoxigenin, glutethim ide, guaiacol, hex-abarbital, hexahydrocannabinol, hexylresorcinol, hippuric acid, homovanillic acid, hydrocortisone,hydromorphon e, hydroq uinone, hydroxy ethyltheophylline, hydroxyindoleacetic acid, hydroxyisoquin-oline, hydroxymethyltestosterone, hydroxynicotinic acid, hydroxyphenobarbital, hydroxyphenylpy-ruvic acid, hydroxyquinoline, ibuprofen, imipramine, indoleacetic acid, indolecarboxaldehyde, indo-me thacin, isobutylm ethylxa nthine, isocarbostyril, isoquinoline-N-oxide, lasix, levorphanol, lidocaine,LSD, meclizine, mefenamate, mefenamic, mefenamic acid, meperidine, mephenesin, mephobarbital,mepivacaine, mescaline, methocarbamal, methoxamine, methoxydichlorobenzoic acid, methyl salic-ylate, methyldopa, methyldopamine, methy lparaben, m ethylphenida te, methylprimidone, methyltes-tosterone, methylxanthine, morphine, nalorphine, naloxone, naltrexol, naphthalene, naphthol, na-phthoylacetic acid, naproxen, nicotine, nicotinic acid, nikethamide, nitrofurantoin, nitrophenol,normethsuximide, oxazepam, oxyphenbutazone, papaverine, paraxanthine, pemoline, pentazocine,pentobarbital, phencyclidine, phenetidine, phenobarbital, phentermine, phenylbutazone, phenytoin,physostigmine, piperonyl butoxide, prednisolone, prednisone, primidone, probenecid, procaine, pro-gesterone, propiomazine, propyl paraben, pyrilamine, pyrithydione, pyrocatechol, quinoline-N-oxide,reserpine, resorcinol, saccharin, salicylamide, salicylate, salicylic, salicylic acid, secobarbital, stano-zolol, sulfacetamide, sulfadimethoxine, sulfaethidole, sulfam erazine, su lfame thazine, sulfamethizole,sulfamethoxazole, sulfanilamide, sulfapyridine, sulfasoxazole, sulindac, testosterone, tetracaine, te-trahydocannabinol, thebaine, theobromine, theophylline, thiamylal, thienylcyclohexylpiperidine,thiobarbituric acid, thiobarbituric, thiosalicylate, thiosalicylic, thiosalicylic acid, tolbutamide, tol-me tin, triamcinolone, trifluoromethylbenzoic acid]

Lurie, LS.; McGuiness, K. The quantitation of heroin and selected basic impurities via reversed phaseHPLC. II. The analysis of adulterated samples. J.Liq.Chromatogr., 1987, 10, 2189-2204 [also im-purities, acetaminophen, acetylcodeine, acetylmorphine, acetylprocaine, aminopyrene, amitriptyline,antipyrene, aspirin, barbital, benztropine, caffeine, cocaine, codeine, diamorphine, diazepam, di-phenhydramine, dipyrone, ephedrine, ethylmorphine, lidocaine, meconin, methamphetamine, meth-apyrilene, methaqualone, monoacetylmorphine, morphine, nalorphine, niacinamide, nicotinamide,noscapine, papaverine, phenacetin, phenmetrazine, phenobarbital, phenolphthalein, procaine, pro-panophenone , propoxyphene, pyrilamine, quinidine, quinine, salicylamide, salicylate, salicylic, sal-icylic acid, secobarbital, strychnine, tetracaine, thebaine, tripelennamine, tropacocaine, vitamin B3,vitamin B5; electrochemical detection]

Wilson, T.D. Recent advances in HPLC analysis of analgesics. J.Liq.Chromatogr., 1986, 9, 2309-2410[also antipyrine, aspirin, buprenorphine, butorphanol, codeine, cyclazocine, diamorphine, dihydro-codeine, etorphine, fentanyl, heroin, hydrocodone, hydromorphone, ibuprofen, LAAM, levorphanol,meperidine, methadone, morphine, nalbuphine, naproxen, oxycodone, oxymorphone, pentazocine,phenacetin, phenazocine, phenylbutazone, propoxyphene, salicylamide, salicylic acid, zomepirac]

Ting, S. Liquid chromatographic determination of levodopa, levodopa-carbidopa, and related impuritiesin solid dosage forms. J.Assoc.Off.Anal.Chem., 1986, 69, 169-173 [simultaneous carbidopa, levodopa;acetaminophen is IS; formulations]Bouquet, S.; Regnier, B.; Quehen, S.; Brisson, A.M.; Courtois, P.; Fourtillan, J.B. Rapid determinationof acyclovir in plasma by reversed phase high-performance liquid chromatography. J.Liq.

Chromatogr., 1985, 8, 1663-1675 [extracted acyclovir; plasma; acetaminophen is IS]


25/26

Wong, S.H.Y.; Marzouk, N.; McHugh, S.L.; Cazes, E. Simultaneous determination of theophylline andcaffeine by reversed phase liquid chromatography using phenyl column. J.Liq.Chromatogr., 1985, 8,1797-1816 [also caffeine, cimetidine, codeine, dimethylxanthine, meperidine, pentobarbital, pheno-barbital, secobarbital, theobromine, theophylline; hydroxyethyltheophylline is IS]Meinsma, D.A.; Radzik, D.M.; Kissinger, RT. Determination of common analgesics in serum and urineby liquid chromatography/electrochemistry. J.Liq.Chromatogr., 1983, 6, 2311-2335 [serum; urine;

electrochemical detection; simultaneous codeine, methyl salicylate, naproxen, phenacetin, salicylicacid]Miner, D.J.; Skibic, M.J.; Bopp, R.J. Practical aspects of LC/EC determinations of Pharmaceuticals inbiological media. J.Liq.Chromatogr., 1983, 6, 2209-2230 [plasma; column-switching; fluorescencedetection; also diethylstilbestrol, enviradene, enviroxime, enviroxine, hexestrol, pergolide,zinviroxime]Ferrell, W.J.; Goyette, G.W. Analysis of acetaminophen and salicylate by reverse phase HPLC.J.Liq.Chromatogr., 1982, 5, 93-96 [also salicylic acid; serum]van der WaI, S.; Bannister, S.J.; Snyder, L.R. Automated analysis of acetaminophen and caffeine inserum using the FAST-LC system: contributions to assay imprecision in procedures based on HPLCwith sample pretreatm ent. J.Chromatogr.Sci., 1982, 20, 260-265 [serum; extracted caffeine, carba-mazepine, phenobarbital, phenylethylmalonamide, phenytoin, primidone, theophylline; cyclobarbitalis IS]Lurie, LS.; Demchuk, S.M. Optimization of a reverse phase ion-pair chromatographic separation fordrugs of forensic interest. II. Factors effecting selectivity. J.Liq.Chromatogr., 1981, 4, 357-374 [alsoacetylcodeine, acetylmorphine, aminopyrene, aminopyrine, amobarbital, amphetamine, antipyrine,benzocaine, butabarbital, caffeine, cocaine, codeine, diamorphine, diazepam, diethylpropion, ephed-rine, glutethimide, lidocaine, mecloqualone, mescaline, methamphetamine, methapyrilene, metha-qualone, methpyrilene, m ethylphenidate, morphine, narcotine, papaverine, pentobarbital, phencycli-dine, phendim etrazine ph enm etrazine, phenob arbital, phenterm ine, phenylpropanolamine, procaine,

quinidine, quinine, secobarbital, strychnine, tetracaine, thebaine, theophylline]Teffera, Y; Abram son, F. Application of high-performance liquid chroma tography/chem ical reaction in-terface mass spectrometry for the analysis of conjugated metabolites: a demonstration using deu-terated acetaminophen. Biol.Mass.Spectrom., 1994, 23, 776-783Osterloh, J.; Yu, S. Simultaneous ion-pair and partition liquid chromatography of acetaminophen, the-ophylline and salicylate with application to 500 toxicologic specimens. Clin.Chim.Acta, 1988, 175,239-248Betowski, L.D.; Korfmacher, W.A.; Lay, J.O.J.; Potter, D.W.; Hinson, J.A. Direct analysis of rat bile foracetaminophen and two of its conjugated metabolites via thermospray liquid chromatography/massspectrometry. Biomed.Environ.Mass.Spectrom., 1987, 14, 705-709Biemer, TA. Simultaneous analysis of acetaminophen, pseudoephedrine hydrochloride and chlorpheni-ramine maleate in a cold tablet using an isocratic, mixed micellar high-performance liquid chromat-ographic mobile phase. J.Chromatogr., 1987, 410, 206-210Colin, P.; Sirois, G.; Ch akr ab arti, S. Rapid high-performance liquid chro ma tographic assay of acetamin-ophen in serum and tissue homogenates. J.Chromatogr., 1987, 413, 151-160Starkey, B.J.; Loscombe, S.M.; Smith, J.M. Paracetamol (acetaminophen) analysis by high performanceliquid chromatography: interference studies and comparison with an enzymatic procedure.Ther.Drug Monit, 1986, 8, 7 8 - 8 4Jung, D.; Zafar, N.U. Micro high-performance liquid chromatographic assay of acetaminophen and its

major metabolites in plasma and urine. J.Chromatogr., 1985, 339, 198-202Mamolo, M.G.; Vio, L.; Maurich, V. High-pressure liquid chromatographic analysis of paracetamol, caf-feine and acetylsalicylic acid in tab lets . Salicylic acid qu antita tion . Farmaco.[Prat]., 1985, 40, 1 1 1 -123To, E.C; Wells, RG. Repetitive microvolumetric sampling and analysis of acetaminophen and its toxi-cologically relevant metabolites in murine plasma and urine using high performance liquid chro-matography. JAnaLToxicol., 1985, 9, 2 1 7 - 2 2 1Das Gupta, V.; Heble, A.R. Quantitation of acetaminophen, chlorpheniramine maleate, dextromethor-phan hydrobromide, and phenylpropanolamine hydrochloride in combination using high-performanceliquid chromatography. J.Pharm.ScL, 1984, 73, 1553-1556


26/26

Krieger, D.J . Liquid chromatographic determina tion of acetaminophen in multicomponent analgesic tab-lets. JAssoc.OffAnaLChem., 1984, 67, 339-341Qu attron e, A. J .; Pu tna m , R.S. A single liquid-chromatographic procedure for ther ap eut ic m onitoring oftheophylline, acetaminophen, or ethosuximide. Clin.Chem., 1981, 27, 129-132West, J.C. Rapid HPLC analysis of paracetamol (acetaminophen) in blood and postmortem viscera.JAnaLToxicoL, 1981, 5, 118-121Das Gupta, V. Simultaneous quantitation of acetaminophen, aspirin, caffeine, codeine phosphate, phe-nacetin, and salicylamide by high-pressure liquid chromatography. J.Pharm.Sci., 1980, 69,110-113

hplc analysis of acetaminophen

Documents