Optimized Gas Chromatography Method for Quantifying Residual Solvents in Clindamycin Phosphate Pledgets: A Comprehensive ICH Q2(R1) Validation Study

Abstract Purpose: Clindamycin phosphate (CP) is widely prescribed for the treatment of anaerobic and gram-positive bacterial infections. Accurate quantification of residual solvents, particularly isopropyl alcohol (IPA), is essential to ensure product safety and compliance with regulatory standards. This study aimed to formulate CP pledgets and to develop and validate a sensitive Gas Chromatography-Flame Ionization Detector (GC-FID) method for IPA determination. Methods: Chromatographic separation was achieved using an Rtx-1301 column under optimized GC-FID conditions, enabling selective detection of IPA without interference from the matrix. The method was validated in accordance with ICH Q2 (R1) guidelines, evaluating linearity, specificity, accuracy, precision, and robustness. Results: The method demonstrated excellent linearity from the LOQ to 200% of the specified limits, with correlation coefficients (R²) of 1.000. Recovery studies confirmed high accuracy (99.1–101.8%), while both method and intermediate precision yielded %RSD values below 15%. Chromatographic performance showed sharp peak resolution and reproducible separation without excipient interference, confirming specificity. Conclusion: The validated GC-FID method provides a reliable, accurate, and robust analytical tool for quantifying IPA in CP pledgets. Its high precision and specificity make it suitable for routine quality control and regulatory compliance, thereby ensuring product safety and efficacy.