Study of Stability Profiles and Development of New Stability Indicating Analytical Methods for Selected Fluoroquinolones

Abstract

Analysis of pharmaceuticals is vital at every stage of development, through the entire newlinejourney that starts with synthesis of a new molecule, and continues through various stages newlineof development, until it is used in the patient. Pharmaceutical Analysis, previously with newlineconventional wet chemistry methods and most recently with sophisticated instrumental newlinetechniques, assures the quality of the product by ensuring acceptance of the product newlinemeeting standards of safety and efficacy. At times, these techniques may need to identify newlineand quantify the drug in presence of other matter, like impurities or degradants, that newlinecoexist due to synthesis process involved or arising due to degradation. The testing newlineprocess needs to be sensitive and specific to establish the content of API in presence of newlinethese impurities and degradants and is also not expected to initiate or promote formation newlineof degradants through conditions that are most conducive to degradation. newlineStability studies meet the objectives of establishing shelf-life and predicting specific newlineconditions for drug degradation. The outcome for such studies provides inputs for newlineadopting good practices that inhibit degradation during the analysis. Application of such newlineprocesses that promote evolution of degradants could lead to misleading results. newlineThe objectives made for the study involved optimization of the experimental conditions newlinethat ensures structural integrity to remain secure and also design an algorithm for newlineprediction of retention with molecules that possess identical or similar structural newlinetemplates. newlineTo meet the objectives, a set of drugs from a single class that has fair potential to get newlineaffected by experimental conditions commonly adopted during analysis like newlineFluoroquinolones (FQs) were considered. The drug candidates chosen for the study werebased on certain pre-set criteria like chemical structure, physicochemical properties and newlinespectrum of activity- ciprofloxacin (CIP), levofloxacin (LEV), moxifloxacin (MOX), newlinenorfloxacin (NOR) and ofloxacin (OFL). newlineDiversity of literature published methods were first assessed with laboratory experiments. newlineNewer HPLC methods were developed, optimized and validated that could be successfully newlineapplied for the drugs bearing common structural templates. Additional LC methods were newlinedeveloped to resolve drug peak from other peaks that were found on application of certain newlineconditions that molecules are exposed to during analysis. LC-MS method was useful in newlineassessing the nature of the degradant that accompanied LEV. The proposed optimized newlineexperimental conditions for the analysis of FQs of research interest have not yielded any newlinedegradants and is recommended for routine analysis. newlineFrom the data mine representing the experimental variables of the LC analysis of FQs of newlineresearch interest, multiple linear regression (MLR) models were designed wherein the newlinereported retention times were mapped to various parameters representing molecular newlinedescriptors. These models could predict the retention time of compounds. The prediction newlinecapability of these models was assessed and statistically validated through application of newlineANOVA. newlineKeywords: RP-HPLC, fluoroquinolones, stability, ICH, retention time, multiple linear newlineregression models.