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.

Recent developments in the determination of residual solvents in pharmaceutical products by microextraction methods

“…8 Among them, the most commonly used technique for the analysis of residual solvents is conventional gas chromatography (GC). 9,10 In order to analyze trace amounts of such analytes in pharmaceuticals, an appropriate sample preparation step is necessary prior to GC. 11,12 The traditional technique for residual solvent determination is direct injection; in which the drug substance or the formulation is dissolved in or extracted with a high boiling point solvent.…”

Validation and optimization of a liquid-phase microextraction method for trace analysis of BTEX in water samples

“…Prior to analysis, for extraction and pre-concentration of target compounds from the aqueous samples, techniques such as liquid-liquid extraction (LLE) and solid-phase extraction (SPE) have been utilized. 11 However, these methods are time-consuming and need large volumes of organic solvents, which are toxic to human health and the environment, and they are also expensive. Solvent free sample preparation methods or those employing less organic solvent are becoming increasingly important and have induced a major advance in analytical methodology.…”

“…Solvent free sample preparation methods or those employing less organic solvent are becoming increasingly important and have induced a major advance in analytical methodology. Purge and Trap (P&T), 6 headspace solid-phase dynamic extraction (HS-SPDE), 4 headspace solid-phase microextraction (HS-SPME), 5,8 headspace 11 or direct aqueous injection (DAI) 10,15 have been reported as alternatives to traditional methods for sample preparation. Liquid phase microextraction (LPME) has been reported as a new method in which low amounts of solvent as extractant are used.…”

Fast Analytical Methodology Based on Mass Spectrometry for the Determination of Volatile Biomarkers in Saliva

“…Sometimes it is not necessary to separate the individual compounds of a sample to resolve the analytical problem in hand, it sufficing to obtain a signal profile of the sample formed by all the components integrating it. 24,25 In this context, different techniques such as ion mobility spectrometry, proton transfer reaction mass spectrometry (PTR-MS), selected ion flow tube mass spectrometry (SIFT-MS), and sensor arrays have addressed the determination of biomarkers. 26À29 Here we propose the use of direct coupling of a headspace sampler (HS) with a mass spectrometer for the rapid determination…”

“…Additionally, a series of separative analyses by GC/MS was performed for confirmatory purposes to show the analytical potential of the nonseparative method. The method based on HS-MS has been previously used for the fast analysis of volatiles in different matrixes including water, 30,31 soil, 32 pharmaceuticals, 25 and food. 33 In this work, five biomarkers (methyl tert-butyl ether (MTBE), dimethyl disulfide, styrene, limonene, and 2-ethyl-1-hexanol) of both diseases and exposure to environmental pollutants were selected to check the possibilities of the proposed methodology.…”