Sensitive determination of arsenite and arsenate in plasma by electrospray ionization tandem mass spectrometry after chelate formation

Inorganic arsenite (As(3+)) and arsenate (As(5+)) are well-known poisons, and the toxicity of As(3+) is about ten times that of As(5+). In this study, a simple, rapid, and sensitive method was developed for As(3+) in plasma using electrospray ionization (ESI) tandem mass spectrometry (MS-MS). After washing plasma with trichloroethylene (TCE), As(3+) in the aqueous layer was reacted with pyrrolidinedithiocarbamate (PDC, C(4)H(8)NCSS(-)), and the produced As(PDC)3 was extracted with methyl isobutyl ketone (MIBK); a 1-A mu l aliquot of the MIBK layer containing As(PDC)(3) was introduced into the MS-MS instrument in the direct-flow injection mode. Other arsenic compounds such as As(5+), monomethyl arsonic acid, dimethyl arsinic acid, arsenobetaine, arsenocholine, and tetramethyl arsonium did not produce As(PDC)(3). Therefore, without liquid chromatographic separation, As(3+) alone could be detected after washing with TCE followed by solvent extraction of As(PDC)(3) with MIBK. Thus, inorganic As(5+) was reduced to As(3+) with thiosulfate, and then the total inorganic As was quantifi ed as As(3+); As(5+)could be calculated by subtracting As(3+)from the total inorganic As. The MS-MS quantification was performed by selected reaction monitoring using a peak at m/z 114 of a product ion (C(4)H(8)NCS)(+) formed by collision-induced dissociation from the precursor ion As(PDC)(2) (+) at m/z 367. The mass spectral identification on MS-MS spectrum was possible even at 1 ng As(3+)/ml plasma. The calibration curve for As(3+) showed linearity from 0.5 to 100 ng/ml plasma. The limits of detection by selected reaction monitoring were 0.3 ng/ml in water and 0.2 ng/ml in plasma. The analysis could be completed in less than 15 min, because chromatographic separation was not necessary before the MS-MS detection.