Analysis of residual solvents in pharmaceuticals with purge-and-membrane mass spectrometry

A method using purge-and-membrane mass spectrometry (PAM-MS) was developed for the analysis of residual solvents in pharmaceutical products. The metho d combines dynamic headspace and membrane inlet mass spectrometry, The limi ts of detection for the compounds studied, benzene, toluene, chloroform, 2- pentene and 2-methyl- and 3-methylpentane, were 0.05-0.1 mg/kg. In quantita tive analysis the method showed good linearity (r(2) > 0.998) and acceptabl e within-day (RSD = 7.9-18%) and between-day (RSD = 6.8-10%) repeatability, The PAM-MS method combined with the custom-made Solver program was compare d with a method using purge-and-trap gas chromatography/mass spectrometry ( P&T-GC/MS) for identification of residual solvents from authentic samples. The results showed that PAM-MS/Solver provides reliable identification of t he main volatile organic compounds (VOCs) in the pharmaceuticals, but VOCs with low concentrations (below 0.5 mg/kg) were better identified by P&T-GC/ MS. Other advantages of the PAM-MS method were short analysis times and non -requirement for pre-treatment of samples, Copyright (C) 2000 John Wiley & Sons, Ltd.