Interference of isonicotinyl hydrazone in the microbiological analysis of rifampicin from anti-tuberculosis FDC products containing isoniazid

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 36; no. 3; pp. 643 - 647
• Main Authors: Mariappan, T.T., Geetha, Thiraviam, Pandey, Rajesh, Jindal, K.C., Singh, Saranjit
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15.11.2004; Elsevier Science
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Antitubercular Agents - metabolism; Antitubercular Agents - pharmacology; Bacillus subtilis - drug effects; Biological and medical sciences; Chemistry, Pharmaceutical; Drug Interactions - physiology; Fundamental and applied biological sciences. Psychology; General pharmacology; Hydrazones - metabolism; Hydrazones - pharmacology; Interference; Isoniazid - metabolism; Isoniazid - pharmacology; Isonicotinic Acids - metabolism; Isonicotinic Acids - pharmacology; Isonicotinyl hydrazone; Medical sciences; Microbiological assay; Microbiological Techniques - methods; Pharmacology. Drug treatments; Rifampicin; Rifampin - metabolism; Rifampin - pharmacology; Microbiological assay; Isonicotinyl hydrazone; Rifampicin; Interference; Infection; Antibiotic; Tuberculosis; Bacteriosis; Antituberculous agent; Mycobacterial infection; Antibacterial agent; Isoniazid
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2004.07.028

Microbiological assay is a sensitive method for the estimation of rifampicin (R). In the present study, interference due to isonicotinyl hydrazone (HYD), an interaction product of R and isoniazid (H), was checked during microbiological analysis of R, employing Bacillus subtilis and Sarcina lutea. The assays were done by disc diffusion method. Both R and HYD showed linear log response curves in the range of 0.01–10 μg. In the presence of HYD, R was overestimated when tested against S. lutea and underestimated in case of B. subtilis. The same extent and type of interference was observed on assay of a marketed anti-tuberculosis fixed-dose combination product, subjected to accelerated stability testing (40 °C/75% RH) for 1 month. This means that response of organisms used in microbiological assay of R might vary in the presence of HYD, with possibility of incorrect conclusions. Therefore, the study suggests that before a microbiological method involving a particular organism is extended to the determination of R in FDC formulations containing H, it should be tested for the influence of HYD and used only if non-interfering.