Abstract
Chemical degradation of drugs often results in altered therapeutic efficacy and can lead to toxic side effects. A single, short and sensitive GC-ECD method for the quantification of degradation and process related impurities of lindane has been developed and validated in all of its pharmaceutical topical dosage forms (shampoo, cream and lotion). Three major degradants were observed during forced degradation (stress stability) studies of lindane dosage forms under various conditions recommended by International Conference on Harmonization (ICH). These were identified and confirmed by using both chemical ionization (CI) and electron ionization (EI) techniques of GC-MS analysis. One major degradation component was identified to be the same as the one that was enhanced during the accelerated and long term stability studies of the dosage forms. A dehydrohalogenation mechanism was proposed for this degradation process, which should considerably ease the pharmaceutical development of lindane dosage forms. The chromatographic conditions were optimized using an impurity-spiked solution and the samples that were generated from forced degradation studies. The best chromatographic separation was achieved on a USP-G27 column using electron capture detector (ECD). The newly developed GC-ECD method was validated with respect to linearity, accuracy, precision and robustness. The limit of detection for the lindane and its impurities were found to be 0.004,0.005,0.005 and 0.004 μg/mL respectively. The accuracy (%recovery) was observed to be 100.0±3.0% for lindane and 100.0±5.0% for its impurities respectively in all-three dosage forms. The current method provides a significant improvement in monitoring stability, quality and therapeutic efficacy of lindane pharmaceutical dosage forms.
Keywords: Forced degradation, GC-ECD, GC-MS, Lindane Lotion, Lindane Shampoo, Method validation
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