HEADSPACE GAS CHROMATOGRAPHY USING FLAME IONIZATION DETECTOR FOR THE VALIDATION OF VOLATILE MIGRANTS AMOUNT IN STOPPERS OF ONCOLOGY DRUG PRODUCT SYSTEMATIC APPROACH

Headspace gas chromatography (HS-GC) methods are highly effective for quantifying volatile migrants in stoppers, as these volatile compounds often contain harmful solvents that require stringent control. However, no HS-GC methods have until now been reported for measuring volatile migrants in the stoppers of oncology drug products. Hence, this study aims to address this gap in the literature by developing a reliable and systematic approach for the detection of volatile migrants in stoppers. A method for analyzing the volatile migrants in stoppers was developed and validated. The analytical method used to determine the volatile migrants amount in stoppers for Melphalan Hydrochloride for Injection 50mg/vial and Sterile Diluent for Melphalan for Injection 10mg/vial by the Headspace Gas Chromatography Flame Ionization Detector method. The validation was performed on Agilent DB-624(30m×0.25 mm×1.4μm) chromatographic column, Inlet Temp 240°C, Split ratio 50:1, Injection volume 1mL, Temperature program 40°C hold 6min,15°C/min heat to 150°C, hold 3min, 20°C/min heat to 240°C, hold 10min, FID Temperature 250°C, Line Temperature 90°C and carrier gas,N2.The validation results of volatile migrants amount in stoppers were linear over the Toluene concentration from 0.0104 µg/mL to 1.2541µg/mL (r = 1.00) and the Toluene recoveries and precision ranged from 97% to 102% (RSD < 10%, n =6). This method was developed and validated successfully, and all the results met the acceptance criteria. Hence, this method is suitable for testing the volatile migrants amount in stoppers of Melphalan Hydrochloride for Injection 50mg/vial and Sterile Diluent for Melphalan for Injection 10mg/vial.