trace element analysis in pharmaceutical products
TRANSCRIPT
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
Analytical Strategy HS2019
Trace Element Analysis in Pharmaceutical Products
10/01/2019 1Gaël Mourouga, Corina Meyer
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
You are an analytical scientist in the trace element team of a contractlaboratory which works largely according to quality standard GMP (goodmanufacturing practice).
Imagine you have nearly unlimited equipment available.
10/01/2019Gaël Mourouga, Corina Meyer 2
Introduction
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
A customer from a large pharmaceutical company comes to you becausethey have a problem with one of their production sites where theyproduce a precious API (active pharmaceutical ingredient):
They have found a hair crack in one of their centrifuges and black,greasy material outside of the container. They contact you for help.
10/01/2019Gaël Mourouga, Corina Meyer 3
Troubleshooting
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
Why is your customer concerned? What are the potentialrisks? Contamination of the API If unnoticed contamination: Toxic effects in patients Reputational damage Financial loss Loss of API Health risk for employees
10/01/2019Gaël Mourouga, Corina Meyer 4
Troubleshooting: Potential Risks
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
What might the dark matter coming out of the centrifuge becomposed of?
10/01/2019Gaël Mourouga, Corina Meyer 5
Troubleshooting: Origin of the Problem
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 6
Troubleshooting: Origin of the Problem
Black color
Normal:
Presence of molybdenum disulphide
Abnormal:
Oxidation due to presence of metallic particles
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 7
Troubleshooting: Origin of the Problem
Leak?
Source: researchgate.net, K.saengchan et al. DOI: 10.1016/j.seppur.2014.02.026
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 8
Troubleshooting: Origin of the Problem
Sealing problem Mechanical problem Lubrication problem
• Leakage from the tanks to the bearings
• Presence of solvent leading to corrosion
• Small deviation of the axis from the vertical position
• Leads to parasitic vibrations, repeated shocks and material fatigue
• Lack of lubrication on the bearings
• Leads to abrasion
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 9
Troubleshooting: Mechanical AnalysisVibration analysis
Source: https://vibralign.com/resources/concepts/vibration-analysis/
Accelerometer Computer Vibration modesVibrations → electric signal Fast Fourier transform Information on rotor
components
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 10
Troubleshooting: Analysis of the «black, greasymaterial»
Bulk analysis: Particle Quantifying Index
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 11
Troubleshooting: Analysis of the «black, greasymaterial»
Magnetic field Ferromagnetic content of the oilperturbation
PQI
Sample
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 12
Troubleshooting: Analysis of the «black, greasymaterial»
OK or slightly increased Increased Extreme
Source: https://www.machinerylubrication.com/Read/296/grease-analysis
High
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 13
Troubleshooting: Analysis of the «black, greasymaterial»
After filtration: Atomic Emission Spectroscopy, Rotrode method
Source: https://en.oelcheck.com/analyses/test-methods/elements-aes-rotrode/
Spectroil Q100
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 14
Troubleshooting: Analysis of the «black, greasymaterial»
Atomic Emission Spectroscopy, Rotrode method
Source: https://en.oelcheck.com/analyses/test-methods/elements-aes-rotrode/
Electric Arc photocellsCrystal latticeHeating40 000 V8000°C
2 mL
Mass of different elements
Light decomposition:wavelength → ray position
Ray intensity → electric current
Range: 1-1000 ppm
Sample
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 15
Troubleshooting: Analysis of the «black, greasymaterial»
AluminumBariumLeadBoron
ChromiumIron
PotassiumCalciumCopperLithium
VanadiumTungsten
Detectable elements:
MagnesiumMolybdenum
SodiumNickel
PhosphorusSilicon
ZincTin
SilverTitanium
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 16
Troubleshooting: Analysis of the «black, greasymaterial»
Analysis of several “normal” samples of lubricant
Average + standard deviation
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 17
Troubleshooting: Analysis of the «black, greasymaterial»
Source: https://www.machinerylubrication.com/Read/296/grease-analysis
OK or slightly increased Increased ExtremeHigh
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 18
Troubleshooting: Analysis of the «black, greasymaterial»
IF calcium and silicon levels are INCREASED to EXTREME
Pollution with lime and dust
IF copper, lead and tin levels are INCREASED to EXTREME
Abrasion
Iron levels
To be coupled with PQI results
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 19
Troubleshooting: Analysis of the «black, greasymaterial»IF PQI is EXTREME
Material fatigue
IF PQI is HIGH and iron levels are OK
Acute wear
IF both PQI and iron levels are INCREASED or HIGH
Normal wear (depending on lifetime)
IF PQI is OK and iron levels are INCREASED or HIGH
Corrosion (rust is not magnetizable)
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 20
Troubleshooting: ConclusionsCorrosion:Most likely comes from sealing problemsBatch analysis should be conducted to assess API pollution
Material fatigue:Most likely comes from a mechanical problemPossible causes include overload of the centrifuge, faulty components, faulty design, …Further investigations should be made and the sealings should be checked
Abrasion:Most likely comes from lack of lubricant or use of the wrong lubricantThe rotor components should be replaced but the batch should be intactNormal wear:An external shock or low quality steel (air bubble) could explain the hair crackThe rotor components should be replaced but the batch should be intact
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
What are key considerations you should focus on as acontract lab?
10/01/2019Gaël Mourouga, Corina Meyer 21
Troubleshooting
Scientific
Verifying and, if possible, cross-validating experiments
Accuracy
Standard procedure
Human
Discretion
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
Provocation: excitation of the sample by applying a form of energy
Reaction: interaction of sample with energy or return tothe ground state
Detection: change caused by the sample
10/01/2019Gaël Mourouga, Corina Meyer 22
General Characterization of Analytical Methods
Provocation Reaction Detection
Source: Lecture Script Analytical Chemistry I + II, Prof. Dr. Detlef Günther, Dr. Peter Lienemann, Beat Aeschlimann, Gisela H. Fontaine, Daniel A. Frick
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
FAAS GFAAS ICP-AES ICP-MS LIBS LA-ICP-MS
Sample liquid liquid liquid liquid solid solid
Limit of detection 0.1 ppm 0.1 ppb 0.001 - 0.1 ppm
ppt - ppb
Precision 1 % 3 % 1 - 2 % 1 %
Linear dynamicmeasuring range
3* 3* 4 - 5* 9*
Amount ofsample
ml μl ml ml
Costs $ $$ $$ - $$$ $$$
Personnelrequisition
low medium medium high
Sample throughput
slow very slow fast fast
10/01/2019Gaël Mourouga, Corina Meyer 23
Overview of Methods
FAAS: Flame Atomic Absorption SpectroscopyGFAAS: Graphite Furnace Atomic Absorption SpectroscopyICP-AES: Inductively Coupled Plasma Atomic Emission Spectroscopy
ICP-MS: Inductively Coupled Plasma Mass SpectrometryLIBS: Laser Induced Breakdown SpectroscopyLA-ICP-MS: Laser Ablation Inductively Coupled Plasma Mass Spectrometry
•Decadic orders of magnitude
Source: N. Lewen, J. Pharmaceut. Biomed., 55 (2011)
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
Nature of the sample matrix Analytical instrumentation available Amount of sample material available Desired analytes Desired method sensitivity Speed of analysis
10/01/2019Gaël Mourouga, Corina Meyer 24
Choice of Method
Source: N. Lewen, J. Pharmaceut. Biomed., 55 (2011)
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 25
Schematic ICP-MS
Source: https://www.researchgate.net/figure/Schematic-of-an-Inductively-Coupled-Plasma-Mass-Spectrometer-ICP-MS_fig5_44226526
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
Different possibilities: Concentric Meinhard nebulizer Cross-flow nebulizer Babington nebulizer V-Groove nebulizer Sharp/GemCone/Burgener nebulizer Microconcentric/Direct injection nebulizer Ultrasonic nebulizer
10/01/2019Gaël Mourouga, Corina Meyer 26
ICP-MS: Nebulizer
Source: Lecture Script Analytical Chemistry I + II, Prof. Dr. Detlef Günther, Dr. Peter Lienemann, Beat Aeschlimann, Gisela H. Fontaine, Daniel A. Frick
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
Nebulizer gas flows around the sample capillary, whose end points to the conic top, generating small droplets
10/01/2019Gaël Mourouga, Corina Meyer 27
Nebulizer: Concentric Meinhard Nebulizer
Source: Lecture Script Analytical Chemistry I + II, Prof. Dr. Detlef Günther, Dr. Peter Lienemann, Beat Aeschlimann, Gisela H. Fontaine, Daniel A. Frick
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
Stability of aerosol yield Size distibution of the droplets Nebulizing efficiency Transport yield Washing out time Memory effect
10/01/2019Gaël Mourouga, Corina Meyer 28
Nebulizer: Things to be aware of
Source: Lecture Script Analytical Chemistry I + II, Prof. Dr. Detlef Günther, Dr. Peter Lienemann, Beat Aeschlimann, Gisela H. Fontaine, Daniel A. Frick
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
Scott chamber Cyclone chamber
The gas stream carrying the droplets is forced to make a abrupt change of direction
Only the small droplets can follow The larger droplets hit the wall and are removed from the
gas stream
10/01/2019Gaël Mourouga, Corina Meyer 29
ICP-MS: Spray Chamber
Source: Lecture Script Analytical Chemistry I + II, Prof. Dr. Detlef Günther, Dr. Peter Lienemann, Beat Aeschlimann, Gisela H. Fontaine, Daniel A. Frick
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 30
ICP-MS: Cyclone Spray Chamber
to ICP
sample
argonwaste
large droplets
small droplets
Source: Lecture Script Analytical Chemistry I + II, Prof. Dr. Detlef Günther, Dr. Peter Lienemann, Beat Aeschlimann, Gisela H. Fontaine, Daniel A. Frick
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
Plasma is created in the torch by an RF generator Torch consists of three concentric tubes: Injector tube: transport of the sample into the plasma Plasma/Intermediate gas: maintains plasma Cooling gas: avoids melting of the torch due to the high
temperature of the plasma (5000 – 8000 K) High temperature of plasma leads to formation of ions
10/01/2019Gaël Mourouga, Corina Meyer 31
ICP-MS: Torch
Source: Lecture Script Analytical Chemistry I + II, Prof. Dr. Detlef Günther, Dr. Peter Lienemann, Beat Aeschlimann, Gisela H. Fontaine, Daniel A. Frick
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 32
ICP-MS: Torch
Source: https://www.researchgate.net/figure/Fassel-type-torch-that-is-typically-used-in-MC-ICP-MS-Approximate-Ar-fl-ow-rates-for-the_fig2_254276358
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
Transfer of ions into vacuum (required for MS) Sampler cone (1 mm hole) Skimmer cone (0.4 mm hole)
Ion optics Extraction of a beam of ions and focussing it to the mass analyzer Separation from UV photons, energetic neutrals and other solid
particles carried into the instrument by the ICP
10/01/2019Gaël Mourouga, Corina Meyer 33
ICP-MS: Trasfer to Vaccum and Ion Optics
Source: Lecture Script Analytical Chemistry I + II, Prof. Dr. Detlef Günther, Dr. Peter Lienemann, Beat Aeschlimann, Gisela H. Fontaine, Daniel A. Frick
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 34
ICP-MS: Trasfer to Vaccum and Ion Optics
from ICP
cones
ion optics
vacuum pumps
quadrupole
Source: https://www.researchgate.net/figure/Schematic-of-an-Inductively-Coupled-Plasma-Mass-Spectrometer-ICP-MS_fig5_44226526
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
Quadrupole MS Sector field MS Time of flight MS
10/01/2019Gaël Mourouga, Corina Meyer 35
ICP-MS: Mass Spectrometry
Source: Lecture Script Analytical Chemistry I + II, Prof. Dr. Detlef Günther, Dr. Peter Lienemann, Beat Aeschlimann, Gisela H. Fontaine, Daniel A. Frick
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
Photomultiplier Faraday cup Daly detector
10/01/2019Gaël Mourouga, Corina Meyer 36
ICP-MS: Detection
Source: Lecture Script Analytical Chemistry I + II, Prof. Dr. Detlef Günther, Dr. Peter Lienemann, Beat Aeschlimann, Gisela H. Fontaine, Daniel A. Frick
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
External calibration Standard addition
10/01/2019Gaël Mourouga, Corina Meyer 37
ICP-MS: Quantification
Source: https://slideplayer.com/slide/2633911/ Source: https://en.wikipedia.org/wiki/Standard_addition
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
Polyatomic interferences: combination of two or moreisotopes from different elements, which usually occur inthe athmospheric plasma
Isobaric interferences: different elements whose isotopesshare a common mass
10/01/2019Gaël Mourouga, Corina Meyer 38
ICP-MS: Interferences
Source: Lecture Script Analytical Chemistry I + II, Prof. Dr. Detlef Günther, Dr. Peter Lienemann, Beat Aeschlimann, Gisela H. Fontaine, Daniel A. Frick
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 39
ICP-MS: Isotope Table Source: Lecture Script Analytical Chemistry I + II, Prof. Dr. Detlef Günther, Dr. Peter Lienemann, Beat Aeschlimann, Gisela H. Fontaine, Daniel A. Frick
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
However, in the overall production process of an API, there might be a range ofsources for “elemental impurities” which need to be controlled.
10/01/2019Gaël Mourouga, Corina Meyer 40
Routine AnalysisA crack in high quality, well-maintained equipment is something, which wouldusually not occur.
Source: http://www.socosur.eu
The International Conference on harmonization of technical requirements forregistration of pharmaceuticals for Human use (ICH) has issued guidelines fordealing with “elemental impurities”, referred to as ICH Q3D.
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
What are “elemental impurities” according to ICH Q3D? Metallic contaminations in drug products The ICH categorized the various elemental impurities infive different classifications: 1, 2A, 2B, 3 and others
10/01/2019Gaël Mourouga, Corina Meyer 41
Routine Analysis: Nature of ElementalImpurities
Source: International Conference on harmonization of technical requirements for registration of pharmaceuticals for human useICH HARMONISED GUIDELINE, GUIDELINE FOR ELEMENTAL IMPURITIES Q3D
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
Class Elements1 As, Cd, Pb, Hg2A Co, Ni, V2B Ag, Au, Ir, Os, Pd, Pt, Rh, Ru, Se, Tl3 Ba, Cr, Cu, Li, Mo, Sb, SnOther elements Al, B, Ca, Fe, K, Mg, Mn, Na, W, Zn
10/01/2019Gaël Mourouga, Corina Meyer 42
Routine Analysis: Classification
Source: International Conference on harmonization of technical requirements for registration of pharmaceuticals for human useICH HARMONISED GUIDELINE, GUIDELINE FOR ELEMENTAL IMPURITIES Q3D
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 43
Routine Analysis: Origin of Elemental Impurities
*see Good Manufacturing Practices (GMP) **see Water Quality Requirements
What might be sources of elemental impurities in aproduction process?
Source: International Conference on harmonization of technical requirements for registration of pharmaceuticals for human useICH HARMONISED GUIDELINE, GUIDELINE FOR ELEMENTAL IMPURITIES Q3D
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 44
Routine Analysis: Potential Sources
Manufacturing equipmentNickel, cobalt, vanadium, molybdenum, chromium, and copper from Hastelloy and stainless-steel alloys
Processing aids/inorganic reagentsProcessing aids such as charcoal, silica, celite, and darco, and inorganic reagents such as sodium chloride, magnesium sulfate, and sodium sulfate
Metal catalystsPalladium and platinum
Source: http://www.pharmtech.com/implementation-ich-q3d-elemental-impurities-guideline-challenges-and-opportunities
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
If you had to estimate to which extent they might come outand how this could be controlled, how would you set up arisk assessment?
10/01/2019Gaël Mourouga, Corina Meyer 45
Routine Analysis: Detection
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 46
Source: http://www.pharmtech.com/implementation-ich-q3d-elemental-impurities-guideline-challenges-and-opportunities
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
If you needed to analyse the Class 1, Class 2B elementsplus the used catalyst Pd for your customer in a drugproduct (tablet), which is prescribed with a max. daily doseof 2 g per day, which method/s would you suggest foranalysis?
10/01/2019Gaël Mourouga, Corina Meyer 47
Routine Analysis
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
Determining the target limit concentration for the analysis:
10/01/2019Gaël Mourouga, Corina Meyer 48
Routine Analysis: Detection
: permitted concentration limit (μg/g)
: Permitted Daily Exposure (μg/day)
: Recommended Daily Intake (2g/day)
Cl Permitted concentration limit (μg/g)
PDE Permitted daily exposure (μg/day)
DI Recommended daily intake (g/day)
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 49
Routine Analysis: DetectionThese are the PDEs for elemental impurities as recommended by the ICH
Source: International Conference onharmonization of technicalrequirements for registration ofpharmaceuticals for human useICH HARMONISED GUIDELINE,GUIDELINE FOR ELEMENTALIMPURITIES Q3D
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 50
Routine Analysis: Detection
Element Class Oral PDE (μg/day)
Cl (μg/g)
Cd, Pb 1 5 2.5As 1 15 7.5Hg 1 30 15Tl 2B 8 4Au, Pd, Ir, Os, Rh, Ru, Pt
2B 100 50
Se, Ag 2B 150 75
Determining target concentrations to analyze:• Classes 1 and 2B only• Oral ingestion (tablet)• Daily intake: 2g/day
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 51
Routine Analysis: Method
Inductively coupled plasma mass spectrometry (ICP-MS)
Advantages Inconvenientsspeed costprecision possible interferences with
other elementssensitivity easy contamination
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 52
Routine Analysis: Method
Source: Reddy et al. , Biomedical and Pharmaceutical Applications of Inductively Coupled Plasma-Mass Spectrometry (ICP-MS), Drug discovery: From concept to market, 2017
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
What would be a suitable sample preparation? Whichconsiderations would be different for Tablet A and B?
10/01/2019Gaël Mourouga, Corina Meyer 53
Routine Analysis
Tablet A Tablet BAPI APIMicrocrystalline cellulose Microcrystalline celluloseHypromellose HypromelloseLactose SorbitolCrospovidone GelatineMagnesium stearateTitanium dioxide
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
Direct Dilution Acid Digestion Solid SampleUltra-high purity solventsrequired
Ultra-high purity acids required No sample preparation needed
Open vessel vs. closed vessel
Microwave assisted
Hot plate
HNO3, HCl, H2SO4, HF, H2O2
10/01/2019Gaël Mourouga, Corina Meyer 54
Sample Preparation
Source: N. Lewen, J. Pharmaceut. Biomed., 55 (2011)
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
What would be a suitable sample preparation? Whichconsiderations would be different for Tablet A and B?
Tablet B: all components organic Tablet A: contains inorganic component (titanium dioxide)
Tablet B: direct dilution or acid digestion Tablet A: acid digestion in a closed vessel (due to Hg)
10/01/2019Gaël Mourouga, Corina Meyer 55
Routine Analysis
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
If your customer wanted to implement analysis of those elements for releaseanalysis, how would you ensure that the method is “valid” to analyse them at thislevel – in compliance with quality standard GMP (good manufacturing practice)?
Precision Accuracy Analytical procedure (SOP) Sensitivity, limit of detection Specificity Repeatability Robustness
10/01/2019Gaël Mourouga, Corina Meyer 56
Routine Analysis
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy
If your customer wanted to implement analysis of those elements for releaseanalysis, how would you ensure that the method is “valid” to analyse them at thislevel – in compliance with quality standard GMP (good manufacturing practice)?
Demonstration of the lack of spectral interferences Demonstrate adequate recovery of analytes Demonstration of precision by determination of RSD Standard addition to demonstrate accuracy of method and adequacy of spikerecoveries Robustness of method by multiple day, multiple analyte and/or multipleinstrument verification of results
10/01/2019Gaël Mourouga, Corina Meyer 57
Routine Analysis
Source: N. Lewen, J. Pharmaceut. Biomed., 55 (2011)
||Trace Element Analysis in Pharmaceutical ProductsAnalytical Strategy 10/01/2019Gaël Mourouga, Corina Meyer 58
Thanks for your attention!
Are there any questions?