ISONIAZID

Isonicotinylhydrazid; INH

C6H7N3O Isoniazid is isonicotinohydrazide. Category: Antitubercular.

Mol. Wt. 137.14

Dose: 300 mg daily or upto 1 g twice weekly. Description: Colourless crystals or white, crystalline powder; odourless. Solubility: Freely soluble in water; sparingly soluble in ethanol (95%); slightly soluble in chloroform; very slightly soluble in ether. Storage: Store in well-closed, light-resistant containers. STANDARDS Isoniazid contains not less than 98.0 per cent and not more than 101.0 per cent of C6H7N3O, calculated with reference to the dried substance. Identification Test A may be omitted if tests B and C are carried out. Test B may be omitted if tests A and C are carried out. A: The infra-red absorption spectrum, Appendix 5.4, is concordant with the reference spectrum of isoniazid or with the spectrum obtained from isoniazid RS. B: Dissolve 0.1 g in 2 ml of water, add a warm solution of 0.1 g of vanillin in 10 ml of water, allow to stand and scratch the inside of the container with a glass rod; a yellow

precipitate is produced. The melting range of the precipitate, after recrystallisation from 5 ml of ethanol (70%) and drying at 105o is between 226o and 231o, Appendix 8.8. C: Melts between 170o and 174o, Appendix 8.8. pH: Between 6.0 and 8.0, determined in a 5.0% w/v solution, Appendix 8.11. Clarity and colour of solution: A 5.0% w/v solution in carbon dioxide-free water is clear, Appendix 6.1, and not more intensely coloured than reference solution BYS7, Appendix 6.2. Heavy metals: Not more than 20 ppm, determined by Method B on 1.0 g, Appendix 3.12. Hydrazine and related substances: Carry out the method for thin-layer chromatography, Appendix 4.6, using silica gel GF254 as the coating substance and a mixture of 50 volumes of ethyl acetate, 20 volumes of acetone, 20 volumes of methanol and 10 volumes of water as the mobile phase. Apply separately to the plate 5 l of each of the following solutions. For solution (1) dissolve 1.0 g of the substance being examined in sufficient of a mixture of equal volumes of acetone and water to produce 10 ml. For solution (2) dissolve 50 mg of hydrazine sulphate in 50 ml of water and dilute to 100 ml with acetone; to 10 ml of this solution add 0.2 ml of solution (1) and dilute to 100 ml with a mixture of equal volumes of acetone and water. After removal of the plate, allow it to dry in air and examine under ultra-violet light (254 nm). Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2). Spray with 4-dimethylaminobenzaldehyde solution dimethylaminobenzaldehyde reagent (amendment 4) and examine in daylight. The additional spot (due to hydrazine) in the chromatogram obtained with solution (2) is more intense than any corresponding spot in the chromatogram obtained with solution (1). Sulphated ash: Not more than 0.1%, Appendix 3.22. Loss on drying: Not more than 0.5%, determined on 1 g by drying in an oven at 105 o, Appendix 8.6. Assay: Weigh accurately about 0.25 g, dissolve in sufficient water to produce 100.0 ml. To 20.0 ml of the resulting solution add 100 ml of water, 20 ml of hydrochloric acid and 0.2 g of potassium bromide and titrate slowly with continuous shaking with 0.0167M potassium bromate using 0.05 ml of methyl red solution as indicator, until the red colour disappears. Each ml of 0.0167M potassium bromate is equivalent to 0.003429 g of C6H7N3O. ISONIAZID TABLETS Isonicotinylhydrazid Tablets; INH Tablets

Usual strengths: 50 mg; 100 mg; 300 mg. Category: Antitubercular. Storage: Store in well-closed, light-resistant containers. STANDARDS Isoniazid Tablets contain not less than 95.0 per cent and not more than 105.0 per cent of the stated amount of isoniazid, C6H7N3O. Identification: A: Shake a quantity of the powdered tablets equivalent to 0.1 g of Isoniazid with 10 ml of ethanol (95%) for 15 minutes, centrifuge and decant the supernatant liquid. Extract the residue with two further quantities, each of 10 ml, of ethanol (95%) and evaporate the combined extracts to dryness. The infra-red absorption spectrum of the residue, Appendix 5.4, is concordant with the reference spectrum of isoniazid or with the spectrum obtained from isoniazid RS. B: Shake a quantity of the powdered tablets equivalent to 1 mg of Isoniazid with 50 ml of ethanol (95%) and filter. To 5 ml of the filtrate add 0.1 g of borax and 5 ml of a 5% w/v solution of 1-chloro-2,4-dinitrobenzene in ethanol (95%), evaporate to dryness on a water-bath and continue heating for a further 10 minutes. To the residue add 10 ml of methanol and mix; a reddish purple colour is produced. Dissolution: Carry out the dissolution test for tablets and capsules, Appendix 7.3, using as the sample 900 ml of water, freshly prepared by distillation, placing one tablet for each test and rotating the paddle at 50 rpm for 45 minutes. Withdraw a suitable volume of the sample and filter promptly through a membrane filter disc having an average pore diameter not greater than 1.0 m, rejecting the first 1 ml of the filtrate. Dilute suitably with water and measure the absorbance of the resulting solution at the maximum at about 263 nm, Appendix 5.5. Calculate the content of C6H7N3O taking 307 as the value of A(1%, 1 cm) at the maximum at about 263 nm. D: Not less than 80% of the stated amount of C6H7N3O. Other requirements: Comply with the requirements of tests stated under Tablets. Assay: Weigh and powder 20 tablets. Weigh accurately a quantity of the powder equivalent to 0.4 g of Isoniazid, dissolve as completely as possible in water, filter and wash the residue with sufficient water to produce 250.0 ml. To 50.0 ml of the resulting solution add 50 ml of water and carry out the Assay described under Isoniazid beginning at the words "20 ml of hydrochloric acid......".