Development of a MSFIA sample treatment system as front end of GC–MS for atenolol and propranolol determination in human plasma

•A semi-automated and sensitive GC–MS method for quantification ATN and PRO in plasma.•The methodology includes a MSFIA system for SPE of ATN and PRO into a RAM precolumn.•On-line derivatization reaction MW-assisted to improve the volatility of analytes.•Multivariate optimization was used to optimize conditions of derivatization reaction.•The methodology was applied to plasma samples from drug users.

An on-line solid-phase extraction (SPE) method coupled to gas chromatography–mass spectrometry (GC–MS) has been developed for the determination of atenolol (ATN) and propranolol (PRO) in human plasma. The hyphenation of SPE with multisyringe flow injection analysis (MSFIA) allows the simultaneous GC–MS determination of ATN and PRO with high selectivity and sensitivity. On-line preconcentration and derivatisation of the analytes were carried out by means of using restricted access materials (RAM) and microwave (MW) assisted derivatisation reactions with N-methyl-N-(trimethylsilyl) trifluoroacetamide (MSTFA)+1% trimethylchlorosilane (TMCS). Multivariate optimization was applied to optimize experimental conditions. The whole procedure comprising sample pretreatment and analyte determination took about 15 min. However, the overlap of the automatic sample treatment with the GC separation increased the frequency to 7 samples h−1. The validated method was successfully applied to direct ATN and PRO determination in human plasma.

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