Analisis Senyawa Barbituratdan Benzodiazepin

Haeria, M.Si

Barbiturates

• All derivatives of Barbituric acid

• Depressants of the central nervous system (CNS) that impair or reduce the activity of the brain by acting as a Gamma Amino Butyric Acid (GABA) potentiators

• Categorized as hypnotics and also called “downers”

• Produce alcohol like symptoms such as impaired motor control (ataxia), dizziness, and slower breathing and heart rate

Sejarah

• Asam barbiturat pertama kali disintesis oleh seorang ilmuwan Jerman bernama Adolf von Baeyer dengan menggabungkan urea dari hewan dengan asam malonat dari apel.

• Pertama kali digunakan sebagai obat untuk menidurkan anjing, tetapi diproduksi sebagai obat tidur pada tahun 1903 yang dikenal sebagai Veronal oleh Bayer.

• Turunan asam barbiturat diresepkan sebagai sedatif, anestetik, anksiolitik, dan antikonvulsan.

Synthesis

Barbituric acid is synthesized by a condensation reaction that results in the release of H2O (dehydration) and the heterocyclic pyrimidine

Further substitution of side chains on the ring produce the pharmacologically active barbiturates

Malonic Acid Urea Barbituric Acid

Types

Barbituric Acid

Amobarbital Phenobarbital Pentobarbital

Ekstraksi

• Triturate a quantity of finely powdered tablet or capsule contents or bulk drug powder with a small amount of methanol sufficient to obtain a solution containing approximately 1 to 20 mg/ml of barbiturate.

• The extract may be used directly or filtered and evaporated to dryness under a stream of nitrogen.

Identifikasi

Dille–Koppanyi reagent modified (a general test for barbiturate–like compounds)

• Reagent:– Larutkan 0,1 g kobalt (II) asetat dihidrat dalam 100 mL metanol.

Tambahkan 0,2 mL asam asetat glasial dan campurkan. – Tambahkan 5 mL isopropilamin dengan 95 mL metanol.

• Method:– Tambahkan 2 tetes larutan 1 pada obat, diikuti dengan

1 tetes larutan 2. • Indications:• Warna ungu cerah (biru-vilet) menunjukkan

adanya senyawa barbiturat.

Mercurous nitrate (general reagent for barbiturate–like compounds)

• Reagent:– Pada larutan pekat merkuri nitrat, tambahkan padatan

natrium bikarbonat hingga terbentuk endapan kuning. Warna endapan kemudian berubah menjadi warna biskuit. Reagen ini harus dibuat segar, kocok sebelum digunakan dan tidak boleh disimpan lebih dari 1 jam.

• Method:– Larutkan sampel dalam sejumlah kecil etanol,

tambahkan 1 tetes ergaen, kocok dan amati selama 2 menit. Lakukan uji blanko.

Mercurous nitrate (general reagent for barbiturate–like compounds)

• Indikasi:– Warna abu-abu gelap menunjukkan adanya cincin

gugus imida atau sulfonamida dengan cincin tambahan,.

Barbital

Mercurous Nitrate—black

Koppanyi–Zwikker Test—violet;

Koppanyi–Zwikker Test—violet;

• Reagent:– Larutan kobalt nitrat 1% b/v dalam etanol

• Method:– Larutkan sampel dalam 1 mL etanol, tambahkan 1

tetes reagen diikuti dengan 10 µL pirolidin, campurkan.

Amobarbital

Mercurous Nitrate—black

Koppanyi–Zwikker Test—violet;

Substruktur

• Barbiturates• Carbonyl Compounds• Carboxylic Acids and Derivatives• Amino Ketones• Ureas and Derivatives• Pyrimidines and Derivatives• Heterocyclic compounds• Carboxamides and Derivatives

Butalbital

Butalbital

• A white crystalline powder. M.p. 138° to 139°.• Slightly soluble in cold water; soluble in boiling

water; soluble in acetone, ethanol, chloroform, ether, and glacial acetic acid; soluble in aqueous solutions of alkali hydroxides and carbonates.

• Colour Tests.– Koppanyi–Zwikker Test—violet; Vanillin Reagent—

orange/colourless.

Vanillin Reagent—orange/colourless.

• Reagen:– Larutkan 1 g vanilin dalam 20 mL asam sulfat,

hangatkan bila perlu.• Metode:– Tambahkan 2 tetes reagen pada sampel, panaskan

di atas w.b suhu 100°C selama 30 detik, catat warna yang terbentuk. Encerkan dengan penambahan beberapa tetes air dan catat warna yang terjadi.

Butobarbital

Butobarbital

• Colourless crystals or white crystalline powder. M.p. 124° to 127°.

• Soluble 1 in 5 alcohol and 1 in 10 ether; practically insoluble in water, insoluble in petroleum ether and aliphatic hydrocarbons.

• Colour Tests.– Koppanyi–Zwikker Test—violet; – Mercurous Nitrate—black.

Phenobarbital

Fenobarbital

• Colourless crystals or a white crystalline powder which may exhibit polymorphism. M.p. 174° to 178°.

• Soluble 1 in 1000 of water, 1 in 8 of ethanol, 1 in 40 of chloroform, 1 in 13 of ether, and 1 in about 700 of benzene.

Fenobarbital natrium

• A white hygroscopic powder, granules, or flakes. M.p. about 175°.

• Soluble 1 in about 1 of water and 1 in about 10 of ethanol; practically insoluble in chloroform and ether.

• Colour Tests.– Koppanyi–Zwikker Test—violet; – Liebermann's Test—red–orange; – Mercurous Nitrate—black.

Pentobarbital

Pentobarbital

• Colourless crystals or a white crystalline powder. M.p. 129° to 130° (from alcohol). A polymorphic form may occur, with an m.p. of about 115°; it gradually reverts to the more stable form on heating at about 110°.

• Very slightly soluble in water; soluble 1 in 4.5 of ethanol, 1 in 4 of chloroform, and 1 in 10 of ether; very soluble in acetone and methanol.

• Colour Tests.– Koppanyi–Zwikker Test—violet; – Mercurous Nitrate—black; – Vanillin Reagent—brown–red/violet.

Secobarbital

Secobarbital

• A white amorphous or crystalline powder. M.p. 100°.

• Very slightly soluble in water; freely soluble in ethanol and ether; soluble in chloroform.

• Colour Tests.– Koppanyi–Zwikker Test—violet; – Mercurous Nitrate—black; – Vanillin Reagent—brown–red/violet.

Benzodiazepin

Benzodiazepin

Ekstraksi

• Triturate a quantity of finely powdered tablet or capsule contents or bulk drug powder with a small amount of methanol sufficient to obtain a solution containing approximately 1 to 20mg/ml of the benzodiazepine.

• The extract may be used directly or filtered and evaporated to dryness under a stream of nitrogen.

Clobazam

Clobazam

• White crystalline powder. M.p. 180° to 182°.• Practically insoluble in water; sparingly soluble

in ethanol; freely soluble in acetone and chloroform.

• Colour Test.– Aromaticity (Method 2)—colourless (heat for

3 min)/red.

Aromaticity (Method 2)

• Tambahkan 2 atau 3 tetes asam nitrit pada sampel, panaskan di atas w.b pada 100°C selama 1 menit, dinginkan campuran. Encerkan 3 atau 4 kali dengan air dan buat larutan menjadi alkali dengan penambahan NaOH 40%.

• Indications:– Perubahan dari tidak berwarna atau kuning dalam

larutan asam menjadi warna lebih gelap (orange atau merah-orange) setelah penambahan NaOH menunjukkan adanya cincin benzen dalam molekul.

Diazepam

Diazepam

• A white or yellow crystalline powder. M.p. 131° to 135°.

• Slightly soluble in water; soluble 1 in 25 of ethanol, 1 in 2 of chloroform, and 1 in 39 of ether.

• Colour Test.– Formaldehyde–Sulfuric Acid—orange.

Formaldehyde–sulfuric acid

• Reagent– Kepada 4 volume asam sulfat tambahkan 6 volume larutan

formaldehid dengan digoyang-goyangkan dan dinginkan. • Metode:

– Campur sampel dengan reagen dan panaskan pada 100°C selama 1 menit.

• Benzodiazepines generally give an orange colour with the exception of bromazepam and clozapine (a benzodiazepine–like compound), which both give yellow, and flurazepam (pink). Other indications include phenothiazines, tetracyclines and thioxanthenes. Tryptamine (brown) and zomepirac (red) also react.

Oxazepam

• A white to pale yellow crystalline powder. M.p. 205° to 206° (crystals from alcohol).

• Practically insoluble in water; soluble 1 in 220 of ethanol, 1 in 270 of chloroform, and 1 in 2200 of ether; soluble in dioxan.

• Colour Test.– Formaldehyde–Sulfuric Acid—orange.