Rapid determination of four short-chain alkyl mercapturic acids in human urine by column-switching liquid chromatography–tandem mass spectrometry

• Determination of short-chain alkyl mercapturic acids in a single chromatographic run.
• Combining sample preparation and analysis by the use of 2D-HPLC–MS/MS.
• Sensitive and specific analysis of short-chain alkyl mercapturic acids in the environmental range.

We developed and validated an analytical method for the simultaneous determination of methyl mercapturic acid (MeMA), ethyl mercapturic acid (EtMA), n-propyl mercapturic acid (PrMA) and iso-propyl mercapturic acid (iPrMA) in human urine. These alkyl mercapturic acids are known or presumed biomarkers of exposure to several alkylating agents including methyl bromide, dimethyl sulfate, ethyl bromide, 1-bromopropane and 2-bromopropane. The method involves a column switching arrangement for online solid phase extraction of the analytes with subsequent analytical separation and detection using liquid chromatography and tandem mass spectrometry. Within day and day-to-day imprecision was determined to range from 4.5 to 12.2%. The analytical method is distinguished by its wide linear working range of up to 2500 μg/L with detection limits ranging from 2.0 μg/L (for PrMA) to 5.1 μg/L (for MeMA) that render possible the application in various biomonitoring studies regarding exposure to alkylating agents. The results of a pilot study on urine samples of 30 individuals occupationally non-exposed to alkylating agents using the new procedure confirmed the background excretion of MeMA (<5.1–35.6 μg/L) and PrMA (<2.0–95.7 μg/L).