Monolithic Spin Column Extraction and GC-MS for Simultaneously Detecting Nine Cold Medication Compounds and the Drug Bromoisovaleryl Urea in Human Serum

Abstract

We describe and validate a gas chromatography-mass spectrometry (GC-MS) method for the simultaneous quantitative detection of nine cold medication compounds and bromoisovaleryl urea an over-the-counter cold medication, in human serum; the nine compounds are acetaminophen (APAP), codeine, dihydrocodeine, three ephedrines, ethenzamide, ibuprofen, and salicylic acid. After adding the internal standard, acetaminophen-d ₄ (APAP-d ₄), compounds were extracted from the serum samples in the monolithic spin column. The extracted samples were evaporated to dryness. The residues were derivatized with acetonitrile and N-methyl-N-(tert-butyldimethylsilyl) trifluoroacetamide + 1% tert-butyldimethylchlorosilane, which were subjected to GC-MS analysis. The limit of quantification (LOQ) was 0.005–0.1 μg mL⁻¹. The calibration curves were linear (r ² > 0.995) in the concentration range from the LOQ to 10 μg mL⁻¹. The intra- and inter-day variations, determined by the measurement of quality control samples at three tested concentrations, showed acceptable values. The lower limit of detection was between 0.005 and 0.05 μg mL⁻¹. Mean recoveries from the serum samples were between 2.5 and 73.8%. This procedure was applied in the toxicological analysis of an intoxicated patient who was responsible for a traffic accident.