Quantitation of methylmalonic acid in serum or plasma using isotope dilution-selected ion gas chromatography-mass spectrometry.

The measurement of plasma or serum methylmalonic acid (MMA) is useful for monitoring therapy in patients with methylmalonic acidemia due to methylmalonyl-CoA mutase deficiency, defects of vitamin B12 metabolism, and also for the determination of functional vitamin B12 deficiency. This method utilizes a stable-isotope labeled internal standard (trideuterated MMA), which is added to the standards, controls, and patient samples prior to extraction. MMA is derivatized by butylation and the amount quantified against a seven-point standard curve using specific selected ions from both the labeled and unlabeled MMA.