Development and validation of a stability-indicative agar diffusion assay to determine the potency of linezolid in tablets in the presence of photodegradation products

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Linezolid (LNZ) is one of the first commercially available (and most widely used) oxazolidinone antibiotics. This study describes the development and validation of a microbiological assay, applying the cylinder-plate method, for the determination of the antibiotic linezolid, as well as the evaluation of the ability of the method in determining the stability of linezolid in tablets. The validation method yielded good results and included linearity, precision, accuracy, robustness and selectivity. The assay is based on the inhibitory effect of LNZ upon the strain of Bacillus subtilis ATCC 9372 used as the test microorganism. The results of the assay were treated statistically by analysis of variance (ANOVA) and were found to be linear (r(2) = 0.9998) in the range of 20-80 mu g mL(-1), precise (inter-assay: R.S.D. = 0.61) and accurate (R.S.D. = 1.7). The method developed and validated proved to be indicative of stability and capable of determining the decay of linezolid in the presence of photodegradation products. Comparison of bioassay and liquid chromatography by ANOVA showed no significant difference between methodologies. The results demonstrated the validity of the proposed bioassay, which is a simple and useful alternative methodology for LNZ determination in routine quality control. (C) 2010 Elsevier B.V. All rights reserved.