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Titration of thiacetazone and isoniazid with sodium methoxide in non-aqueous medium
~39-9l40/82/0l0057-0I M3.co/0 Pergamon Press Ltd
Tulonru, Vol 29, p. 57. 1982 Printed m Great Britain
TITRATION OF THIACETAZONE AND ISONIAZID WITH SODIUM METHOXIDE IN NON-AQUEOUS MEDIUM ANUPA DAS and K. S. BOPARAJ School
of Studies
in Chemistry, Vikram University, Ujjain, 456010, M.P., India
(Received 2 September 1980. Revised 23 May 1981. Accepted 2 June
Summary-Thiacetazone
and isoniazid dissolved in dimethylformamide
sodium methoxide in benzene-methanol cylate does not interfere.
mixture,
with o-nitroaniline
1981)
can be accurately as indicator. Sodium
titrated with 4-aminosali-
RESULTS
Iodometric determination of thiacetazone’ is rather sensitive to variation in the amount of reagents, reaction time and temperature. Iodometry’ based on the oxidation of thiacetazone to the semicarbazone is preferable to the method involving oxidation to the thiadiazole with ferric chloride in sulphuric acid medium, because of its practicality. Oxidation with alkaline hydrogen peroxide3 is rather time-consuming. Gravimetric estimation4 as the 2,4_dinitrophenylhydrazone gives low recovery but the argentimetric method5*6 is satisfactory. Other methods include acidimetric titraalkalimetric determination of acetic acid tion’, formed by hydrolysis,* and mercurimetricg and spectrophotometric determinations. Thiacetazone can be titrated in dimethylformamide medium with sodium methoxide solution in benzene-methanol, o-nitroaniline being used as indicator. This method offers the advantage over acidimetric determination’ that it is unaffected by sodium 4-aminosalicylate, but isoniazid interferes quantitatively. Determination of isoniazid in this way is better than the alkalimetric determination” in diethylamine medium. The end-points are sharp and stable for more than 5 min.
The mean recovery for 49.9 mg of thiacetazone was 49.95 mg, standard deviation 0.14 mg (five replicates). The corresponding results for isoniazid (50.0 mg) were 49.8 mg and 0.13 mg. When x mg of a mixture of pure thiacetazone (Y mg) and isoniazid were titrated with V ml of sodium methoxide (molarity M), and the results were evaluated by means of the equation 236x - 32332VM Y=
99
the recovery of both drugs 995lOO.So/;, (15 replicates).
was
in
the
range
Acknowledgements-The authors are grateful to C.S.I.R. (India) for the award of a research fellowship (to A.D.) and to Professor M. M. Bokadia for providing research facilities. REFERENCES 1. Yu-Wen Sung,. Yao Hsueh Hsueh Pao, 1960, S, 232. and U. Wappler, Zentralbl. 2. P. Pflegel, E. Liidtke Pharm. Pharmakotherapie Laboratoriumsdiagnostik, 1971, 110,673. 3. E. N. Zelenina, Farmafsiyu (Moscow), 1969, 18, No. 3, 78. 4. K. Nagasawa and S. Ohkuma. J. Pharm. Sot. Japan, 1954, 14, 410. 5. E. A. Haugas and B. W. Mitchell, J. Pharm. Pharmaco/., 1956, 2, 259. Suddeut. Apoth-Ztg., 1950, 90, 804. 6. R. Middeldorf, 7. M. B. Devani and C. J. Shishoo, Indian J. Pharm., 1967, 29, 307. 8. T. Sudo, D. Shimoe and T. Tsuju, Bunseki Kagaku, 1957, 6, 494. 9. L. M. Bazhina and G. I. Kudymov, Deposited Doe., 1979, VINITI 893-79. 10. A. Anastasi, E. Mecarelli and L. Novacic, Mikrochem. Mikrochim. Acta, 1953, 40, 53. 11. T. Canblck, J. Pharm. Pharmacol., 1952, 4, 407.
EXPERJMENTAL Procedure A weighed quantity of thiacetazone or isoniazid is dissolved in 25 ml of dimethylformamide. o-Nitroaniline (2 drops of 1% solution in benzene) is added and the solution is titrated with sodium methoxide solution in benzenemethanol (4: 1) to a distinct orange colour. Blanks are run on the same volume of solvent, and their value deducted, For a sharp end-point the molarity of the sodium methoxide (0.05, 0.075 and O.lM for thiacetazone, the binary mixture and isoniazid respectively) should be chosen so that the volume used in the titration does not exceed 8 ml.
57
Tulonru, Vol 29, p. 57. 1982 Printed m Great Britain
TITRATION OF THIACETAZONE AND ISONIAZID WITH SODIUM METHOXIDE IN NON-AQUEOUS MEDIUM ANUPA DAS and K. S. BOPARAJ School
of Studies
in Chemistry, Vikram University, Ujjain, 456010, M.P., India
(Received 2 September 1980. Revised 23 May 1981. Accepted 2 June
Summary-Thiacetazone
and isoniazid dissolved in dimethylformamide
sodium methoxide in benzene-methanol cylate does not interfere.
mixture,
with o-nitroaniline
1981)
can be accurately as indicator. Sodium
titrated with 4-aminosali-
RESULTS
Iodometric determination of thiacetazone’ is rather sensitive to variation in the amount of reagents, reaction time and temperature. Iodometry’ based on the oxidation of thiacetazone to the semicarbazone is preferable to the method involving oxidation to the thiadiazole with ferric chloride in sulphuric acid medium, because of its practicality. Oxidation with alkaline hydrogen peroxide3 is rather time-consuming. Gravimetric estimation4 as the 2,4_dinitrophenylhydrazone gives low recovery but the argentimetric method5*6 is satisfactory. Other methods include acidimetric titraalkalimetric determination of acetic acid tion’, formed by hydrolysis,* and mercurimetricg and spectrophotometric determinations. Thiacetazone can be titrated in dimethylformamide medium with sodium methoxide solution in benzene-methanol, o-nitroaniline being used as indicator. This method offers the advantage over acidimetric determination’ that it is unaffected by sodium 4-aminosalicylate, but isoniazid interferes quantitatively. Determination of isoniazid in this way is better than the alkalimetric determination” in diethylamine medium. The end-points are sharp and stable for more than 5 min.
The mean recovery for 49.9 mg of thiacetazone was 49.95 mg, standard deviation 0.14 mg (five replicates). The corresponding results for isoniazid (50.0 mg) were 49.8 mg and 0.13 mg. When x mg of a mixture of pure thiacetazone (Y mg) and isoniazid were titrated with V ml of sodium methoxide (molarity M), and the results were evaluated by means of the equation 236x - 32332VM Y=
99
the recovery of both drugs 995lOO.So/;, (15 replicates).
was
in
the
range
Acknowledgements-The authors are grateful to C.S.I.R. (India) for the award of a research fellowship (to A.D.) and to Professor M. M. Bokadia for providing research facilities. REFERENCES 1. Yu-Wen Sung,. Yao Hsueh Hsueh Pao, 1960, S, 232. and U. Wappler, Zentralbl. 2. P. Pflegel, E. Liidtke Pharm. Pharmakotherapie Laboratoriumsdiagnostik, 1971, 110,673. 3. E. N. Zelenina, Farmafsiyu (Moscow), 1969, 18, No. 3, 78. 4. K. Nagasawa and S. Ohkuma. J. Pharm. Sot. Japan, 1954, 14, 410. 5. E. A. Haugas and B. W. Mitchell, J. Pharm. Pharmaco/., 1956, 2, 259. Suddeut. Apoth-Ztg., 1950, 90, 804. 6. R. Middeldorf, 7. M. B. Devani and C. J. Shishoo, Indian J. Pharm., 1967, 29, 307. 8. T. Sudo, D. Shimoe and T. Tsuju, Bunseki Kagaku, 1957, 6, 494. 9. L. M. Bazhina and G. I. Kudymov, Deposited Doe., 1979, VINITI 893-79. 10. A. Anastasi, E. Mecarelli and L. Novacic, Mikrochem. Mikrochim. Acta, 1953, 40, 53. 11. T. Canblck, J. Pharm. Pharmacol., 1952, 4, 407.
EXPERJMENTAL Procedure A weighed quantity of thiacetazone or isoniazid is dissolved in 25 ml of dimethylformamide. o-Nitroaniline (2 drops of 1% solution in benzene) is added and the solution is titrated with sodium methoxide solution in benzenemethanol (4: 1) to a distinct orange colour. Blanks are run on the same volume of solvent, and their value deducted, For a sharp end-point the molarity of the sodium methoxide (0.05, 0.075 and O.lM for thiacetazone, the binary mixture and isoniazid respectively) should be chosen so that the volume used in the titration does not exceed 8 ml.
57