Electrospray ionization tandem mass spectrometric determination of monomethylarsonic acid and dimethylarsinic acid after adduct formation with citric acid

Inorganic arsenic species are metabolized to monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV) and excreted into urine. A simple, rapid and sensitive method has been developed using electrospray ionization tandem mass spectrometry (ESI-MS–MS) for the simultaneous determination of MMAV and DMAV. MMAV and DMAV in a sample were allowed to react with citric acid (CiA). Adduct compounds were extracted together with isoamyl alcohol (IAA). An aliquot (1-μL) of the IAA layer was directly injected into the ESI-MS–MS instrument, and was detected within 1 min. Quantification was done using selected reaction monitoring for MMAV and DMAV as follows:[MMAH + 2CiA − 3H2O]+ → [MMAH + CiA − 2H2O]+[DMAH + CiA + MeOH − 2H2O]+ → [DMAH + MeOH − H2O]+where MMAH and DMAH denote the protonated forms of MMAV and DMAV, and MeOH denotes methanol (carrier liquid in ESI-MS–MS). This method was validated for the analysis of urine samples. The limit of detection of As was 0.3 μg L−1 for MMAV and 0.6 μg L−1 for DMAV using 10 μL of sample solution. Results were obtained in <10 min with a linear calibration range of 3–100 μg L−1. Inorganic arsenic compounds (and other organic arsenic compounds) found in urine did not interfere with the detection of MMAV and DMAV. Concentrations of MMAV and DMAV in the reference urine SRM 2670a were estimated after partial purification, and those in urine of a patient treated with As2O3 were measured after dilution.