Development and Validation of Stability Indicating Analytical Methods for Antibiotic Drug Substances

Abstract

Stability of a drug or product is defined as its ability to maintain its physical, chemical, microbiological and therapeutic values throughout its period of storage and use. The safety of a drug is not only determined by its pharmacological or toxicological profile but also the adverse effects caused by the impurities (IMPs) and/or degradation products (DPs) in its course of storage till its expiry date. Hence; stability assessment of pharmaceutical products with respect to their purity, quality and efficacy is important. The drug molecules selected for the study belong to the class of fluoroquinolone (FLQ) antibiotic drugs. FLQs are widely used and are an important class of antibiotics, because of their broad spectrum antibacterial activity. Some of the FLQ drugs have also shown potential antimalarial activity revealing their significance in the therapeutic use. Apart from their clinical or pharmacological significance, FLQ drugs are also known for their potential toxicological effects.The aim of the study was to evaluate degradation profiles of four FLQ antibiotic drugs namely Pazufloxacin, Nadifloxacin, Besifloxacin and Sparfloxacin for development and validation of stability indicating analytical methods. All selected drugs were subjected to forced degradation studies. The drug Pazufloxacin was found labile only to acid hydrolysis forming two degradants. The gradient RP-HPLC method was developed and validated successfully. The degradants were identified by LC-MS studies wherein, the DPs were formed as a result of decarboxylation and esterification of the drug. Nadifloxacin was found to be labile to acid hydrolysis and reduction degradation forming a total of nine DPs which were separated from the drug by a gradient RP- HPLC method. The degradants formed under acidic conditions were characterized by LC-MS analysis. In case of Besifloxacin, five DPs were formed as degradation was observed under photolytic degradation, oxidative degradation, acid and base hydrolysis