An improved assay for plasma methylmalonic acid using chemical ionization gas chromatography mass spectrometry

Objectives To develop a precise and sensitive assay for methylmalonic acid (MMA) using positive chemical ionization gas chromatography mass spectrometry (CI GC-MS), and to illustrate its clinical utility. Methods Using the developed assay, reference intervals were determined with 108 ambulatory individuals, and potential clinical utility examined in 178 consecutive patients with possible cobalamin deficiency (serum B12< 200 nmol/L). Results and conclusions Methylmalonic acid measured by CI GC-MS was precise (CV: 4–5%), and sensitive (limit of quantitation: 37 nmol/L). In a clinical reference set, 37% of individuals with serum B12 less than 200 pmol/L had plasma MMA concentrations within the reference interval (75–378 nmol/L), rendering cobalamin deficiency unlikely. The observation illustrates that MMA assay may be a useful adjunct test in assessing patients with low serum B12.