Use of Mass Spectrometry Methods as a Strategy for Detection and Determination of Residual Solvents in Pharmaceutical Products

Abstract

In the present work a strategy for the qualitative and quantitative analysis of residual solvents in pharmaceutical products is reported. First, a low-resolution chromatogram is generated for the identification of the solvents present in the samples by means of headspace generation-fast gas chromatography-mass spectrometry (HS-fast GC/MS). From the plotting of this information by means of contour plots with time and mass/charge axes, it is decided whether quantification of such compounds can be accomplished without chromatographic separation or whether it should be done by fast gas chromatography. The nonseparative method is based on direct coupling of a headspace sampler with a mass spectrometer (HS-MS) and requires a signal recording time of only 3 min, while with fast gas chromatography the time required to obtain a chromatogram is 7.16 min. The use of headspace generation for introducing the sample and standard addition as a quantification technique provided satisfactory results and minimized the matrix effect. An important advantage of the methodologies used here is related to the fact that no prior treatment of the sample is required, thus minimizing the creation of analytical artifacts and the errors associated with this step of the analytical process. The methods were applied to the determination of residual solvents in 27 different pharmaceutical products. Detection and quantitation limits were sufficiently low to enable the estimation of organic volatile impurities according to the International Conference on Harmonization (ICH) of Technical Requirements for the Registration of Pharmaceuticals for Human Use.