DETERMINATION OF DICHLOROACETATE AND ITS METABOLITES IN HUMAN PLASMA BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY

Sodium dichloroacetate (DCA) is an investigational drug for the treatm ent of lactic acidosis, and is also a putative environmental toxicant. We developed and validated a gas chromatography-mass spectrometry (GC -MS) technique that simultaneously measures lactate, DCA and its metab olites, monochloroacetate (MCA), glyoxylate, glycolate and oxalate in human plasma. Following administration of [C-13(1,2)]DCA to healthy vo lunteers, blood samples were collected at various time points and the drug and its metabolites present in plasma were derivatized to their m ethyl esters by reacting with 12% boron trifluoride-methanol complex. The methyl esters were extracted with methylene chloride and analyzed by GC-MS. The quantitation limits of DCA and metabolites ranged betwee n 0.3 and 1.5 mu M. The coefficients of variation of the standards wit hin the entire calibration range were between 0.3 and 14.5%. The bias values ranged between -16.3% and 18.7%. Total recoveries from derivati zation and extraction were between 46.9% and 78.5%. The coefficients ( r(2)) of linear regression of the calibration curves were 0.9882 to 0. 9996. (C) 1997 Elsevier Science B.V.