Determination of Residual Methyl Iodide in Tedizolid Phosphate and Alogliptin Benzoate by Static Headspace Gas Chromatography With Electron Capture Detection

Abstract

Methyl iodide has been highlighted as a potential genotoxic impurity (PGI). A sensitive HS-GC method with ECD was developed and validated for the determination of methyl iodide impurity in Tedizolid phosphate, an active pharmaceutical ingredient. HS-GC method on DB-624,column 60m X 0.53mm, film thickness 3μm, with electron capture detector (ECD) was used. The proposed method was specific, linear, accurate, rugged and precise. The calibration curves showed good linearity over the concentration range of 0.78 μg/g to 11.7 μg/g and the correlation coefficient was 0.997. Method had very low limit of detection (LOD) and limits of quantification (LOQ) are 0.23 μg/g and 0.78 μg/g, respectively, with respect to test concentration. Accuracy was observed within the range 96.0% to 103.2%. This method is a further extended good quality control tool for low level quantitation of methyl iodide impurity in another API, alogliptin benzoate.

Development and Validation of Headspace-Gas Chromatography (HS-GC) Method for the Determination of Potential Genotoxic Impurities in Meloxicam

“…The linearity study demonstrated a strong linear relationship between the theoretical and concentrations of genotoxic impurities were obtained with the regression coefficients (R) 0.999 for propionaldehyde, 2-chloropropanol, chloromethane and 1 for isopropylchloride compounds. These results are consistent with prior works 27,31,32 which reported the linearity of Headspace-Gas Chromatography methods for the analysis of pharmaceutical compounds. The accuracy assessment involving spiking the genotoxic impurities at different levels showed good recovery percentages, falling within the acceptable range of 80-120% of the limit level.…”