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

Abstract

A method using purge-and-membrane mass spectrometry (PAM-MS) was developed for the analysis of residual solvents in pharmaceutical products. The method combines dynamic headspace and membrane inlet mass spectrometry. The limits 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 quantitative analysis the method showed good linearity (r(2) > 0.998) and acceptable 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 compared 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 the 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.

High surface area membrane introduction mass spectrometry for analysis of volatile and semi‐volatile organic compounds in air

“…This method is utilized in gathering on‐line diagnostic data from complex mixtures present in air or water, such as those found in reacting chemical streams,1,, 2 environmental samples3,, 4 and pharmaceutical intermediates 5,. 6 Exposure of the sample stream to a semi‐permeable membrane can be used to selectively introduce compounds present in a fluid matrix into the mass spectrometer. The process is considered to occur in three steps: (i) selective adsorption of analyte at the membrane surface, (ii) permeation through the membrane, and (iii) desorption into vacuum, or into a gaseous carrier stream such as helium 7–9…”

Dynamic calibration and dissolved gas analysis using membrane inlet mass spectrometry for the quantification of cell respiration

“…By combining the quadrupole mass spectrometer with a membrane inlet system for sample introduction, dissolved gaseous and volatile substances and their dynamics can be accurately and quickly characterized 5,7–9. Membrane inlet mass spectrometry (MIMS) has been widely used and become increasingly popular in various scientific fields such as clinical, pharmaceutical, environmental and analytical applications, and biotechnology 10–13. The advantage of using the MIMS for dissolved gas analysis over the other analysis techniques is that the detection of various kinds of compounds is performed by means of a single probe.…”