Determination of dichloroacetate and its metabolites in human plasma by gas chromatography-mass spectrometry.
Sodium dichloroacetate (DCA) is an investigational drug for the treatment 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 metabolites, monochloroacetate (MCA), glyoxylate, glycolate and oxalate in human plasma. Following administration of [13C1,2]DCA to healthy volunteers, blood samples were collected at various time points and the drug and its metabolites present in plasma were derivatized to their methyl 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 between 0.3 and 1.5 microM. The coefficients of variation of the standards within the entire calibration range were between 0.3 and 14.5%. The bias values ranged between -16.3% and 18.7%. Total recoveries from derivatization and extraction were between 46.9% and 78.5%. The coefficients (r2) of linear regression of the calibration curves were 0.9882 to 0.9996.
Yan
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Z
Department of Medicine (Division of Endocrinology and Metabolism), College of Medicine, University of Florida, Gainesville 32610, USA.
Henderson
G N
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James
M O
MO
Stacpoole
P W
PW
D000284:Administration, Oral; D000328:Adult; D002247:Carbon Isotopes; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D003999:Dichloroacetic Acid / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism; D004952:Esters; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D007275:Injections, Intravenous; D019344:Lactic Acid / Q000097:blood* / Q000378:metabolism; D016014:Linear Models; D008297:Male; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D002247:Carbon Isotopes; D004952:Esters; D019344:Lactic Acid; D003999:Dichloroacetic Acid