Comparison of two methods for measuring methylmalonic acid as a marker for vitamin B12 deficiency

Abstract

Background: Methylmalonic acid (MMA) is a functional marker of vitamin B12 status and a valuable diagnostic tool. The gas chromatography mass spectrometry (GCMS) MMA assay has been used for decades in clinical studies. Methods: In this study, we compared a newly developed liquid chromatography tandem mass spectrometry assay for MMA (ClinMass ® Complete Kit) with the GCMS method and further measured other relevant vitamin B12 markers (homocysteine, total B12 and holotranscobalamin) to validate the new liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) method. For this purpose, 138 samples that were sent to our routine laboratory total B12 assay were used. Results: The GCMS and LC-MS/MS assays showed a strong correlation (r = 0.92, p < 0.001) particularly at low holoTC levels (deficiency is more probable). Forty six cases had MMA > 300 nmol/L with both methods. Only five subjects showed MMA GCMS > 300 nmol/L, but MMA LC-MS/MS ≤ 300 nmol/L. However, the LC-MS/MS method showed a slightly better correlation with other B12 markers (holoTC, total B12). In addition, the LC-MS/MS method offers several advantages over the GCMS method, such as saving time and costs, precision, flexibility and popularity in modern labs. Conclusions:The new LC-MS/MS assay for MMA showed an excellent correlation to the GCMS method. The two methods showed similar agreements with other vitamin B12 markers.

A facile and economic electrochemical sensor for methylmalonic acid: a potential biomarker for vitamin B12 deficiency

“…11 The primitive assays that made use of gas chromatography 10 failed to provide encouraging results, which led to a major improvement by the adoption of comparative studies using GC-MS and LC-MS/MS techniques. 12 Moreover, the HPLC method 13 and UPLC-M/MS 14 have also been employed for the detection of MMA. Despite the utilisation of several chromatographic and analytical instrumental techniques, electrochemical sensing displays a greater level of application potential due to its less labour-intensive, reliable, and extensive properties.…”

Cancer Biomarker Methylmalonic Acid Detection by Molecularly Imprinted Polyaniline Paper Sensor

“…Many methods have been developed to detect MMA. Clinical determination of MMA concentration is by the method of gas chromatography mass spectroscopy (GCMS) or liquid chromatography mass spectroscopy (LCMS) [5,6]. However, these methods require extensive sample pre-treatment and large sample volume.…”

A novel Co(ii)-based MOF with selective fluorescence as a turn-on sensor for biomarker methylmalonic acid

“…Extensive efforts have been devoted to studying a number of methods for the detection of MMA, such as the high-performance liquid chromatography (HPLC) method, and (ultra-performance) liquid chromatography-tandem mass spectroscopy ((UP)LC-MS/MS) 10–14 However, these techniques are not exactly convenient due to the complexity of the analysis processes. 15 Fabricating a facile detection method with high selectivity is very essential to accurately detect MMA in urine or serum.…”

“…7,8 The detection of MMA has another important role as it can be utilized to analyse methylmalonic acidemia, a genetic condition that occurs in infants and could result in severe toxicity and other health issues. 9 Extensive efforts have been devoted to studying a number of methods for the detection of MMA, such as the highperformance liquid chromatography (HPLC) method, and (ultra-performance) liquid chromatography-tandem mass spectroscopy ((UP)LC-MS/MS) [10][11][12][13][14] However, these techniques are not exactly convenient due to the complexity of the analysis processes. 15 Fabricating a facile detection method with high selectivity is very essential to accurately detect MMA in urine or serum.…”