Highly sensitive and selective measurement of underivatized methylmalonic acid in serum and plasma by liquid chromatography-tandem mass spectrometry

Yuan, Chao; Gabler, Jessica; El-Khoury, Joe M.; Spatholt, Regina; Wang, Sihe

doi:10.1007/s00216-012-6099-z

Cited by 18 publications

(18 citation statements)

References 20 publications

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“…3). This was generally consistent with other reports [11, 18], however Kushnir et al reported an interference with the citrate tube, causing a significant increase of the confirmation ion ratio [11]. …”

Section: Resultssupporting

confidence: 93%

“…We confirmed previous reports [16, 18] that MMA was stable for up to three freeze/thawing cycles and for up to one week of serum storage at room temperature (data not shown). Given these results, it was not surprising that the short-term stability of MMA in extracted samples (3 days at 7 °C and 1 week at −20 °C) was also very good (± 3 % and ± 1%, respectively from the original value).…”

Section: Resultssupporting

confidence: 92%

“…The use of an isotopically-labeled ISTD is expected to correct for any loss of analyte during sample handling. The high accuracy assessed through spike recovery for the LC-MS/MS method (94% ± 5.5%) was comparable to that reported for the GC/MS method (96% ± 1.9%, [19]) and to other LC-MS/MS methods [10–18]. Our LC-MS/MS method also achieved a good extraction efficiency of 81%, as assessed from post-extraction addition of ISTD.…”

Section: Resultssupporting

confidence: 76%

“…Our LC-MS/MS method achieved good precision with a total CV of 4.9–7.9% for three serum QC pools analyzed over 22 runs (Table 2), similar to the precision of the GC/MS method (CV of 5.4 % for three plasma QC pools analyzed over 56 runs, [19]) and to other LC-MS/MS methods [10–18]. We can rate our method precision more objectively by using generally applicable quality goals based on biologic variation [28].…”

Section: Resultssupporting

confidence: 63%

“…This makes direct analysis by GC/MS challenging and various types of derivatization (silylation, cyclohexanol, chloroformate and butanol) have been reported to improve detection [6–9]. LC-MS/MS methods [10–18], yield shorter run times and better sensitivity compared to GC/MS procedures. These two factors are critical when a method is used for population monitoring because they translate to higher throughput and lower patient sample volume.…”

Section: Introductionmentioning

confidence: 99%

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An LC-MS/MS method for serum methylmalonic acid suitable for monitoring vitamin B12 status in population surveys

et al. 2014

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Methylmalonic acid (MMA), a functional indicator of vitamin B12 insufficiency, was measured in the U.S. population in the National Health and Nutrition Examination Survey (NHANES) from 1999–2004 using a GC/MS procedure that required 275 µL of sample and had a low throughput (36 samples/run). Our objective was to introduce a more efficient, yet highly accurate LC-MS/MS method for NHANES 2011–2014. We adapted the sample preparation with some modifications from a published isotope-dilution LC-MS/MS procedure. The procedure utilized liquid-liquid extraction and generation of MMA di-butyl ester. Reversed-phase chromatography with isocratic elution allowed baseline resolution of MMA from its naturally occurring structural isomer succinic acid within 4.5 min. Our new method afforded an increased throughput (≤160 samples/run) and measured serum MMA with high sensitivity (LOD = 22.1 nmol/L) in only 75 µL of sample. Mean (±SD) recovery of MMA spiked into serum (2 days, 4 levels, 2 replicates each) was 94±5.5%. Total imprecision (41 days, 2 replicates each) for three serum quality control pools was 4.9–7.9% (97.1–548 nmol/L). The LC-MS/MS method showed excellent correlation (n=326, r=0.99) and no bias (Deming regression, Bland-Altman analysis) compared to the previous GC/MS method. Both methods produced virtually identical mean (±SD) MMA concentrations [LC-MS/MS: 18.47±0.71 ng/mL (n=17), GC/MS: 18.18±0.67 ng/mL (n=11)] on a future plasma reference material compared to a GC/MS method procedure from the National Institute of Standards and Technology [18.41±0.70 ng/mL (n=15)]. No adjustment will be necessary to compare previous (1999–2004) to future (2011–2014) NHANES MMA data.

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Section: Resultssupporting

confidence: 93%

Section: Resultssupporting

confidence: 92%

Section: Resultssupporting

confidence: 76%

Section: Resultssupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

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An LC-MS/MS method for serum methylmalonic acid suitable for monitoring vitamin B12 status in population surveys

et al. 2014

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Development and validation of a simple HPLC‐MS/MS method for the quantification of methylmalonic acid in human serum without a derivatization step

Hofmann¹,

Gebauer²,

Krnáč

et al. 2023

Biomedical Chromatography

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A simple and rapid HPLC-MS/MS analytical method was developed and validated for the determination of methylmalonic acid (MMA) in human serum without a derivatization step. Serum samples (200 μl) were pretreated using a simple method based on ultrafiltration using a VIVASPIN 500 ultrafiltration column. Chromatographic separation was achieved on a Luna Omega C18 column with a PS C18 precolumn guard by gradient elution using 0.1% (v/v) formic acid in water (mobile phase A) and 0.5% (v/v) formic acid in acetonitrile (mobile phase B) at a flow rate of 0.2 ml min À1 . The total run time of the analysis was 4.5 min. Negative electrospray ionization and multiple reaction monitoring mode were used. The lower limit of detection and lower limit of quantification for MMA were determined to be 13.6 and 42.3 nmol L À1 , respectively.The developed method enabled the quantification of MMA in a wide linear range of 42.3-4230 nmol L À1 with a correlation coefficient of 0.9991.

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LC–MS/MS Method for High-Throughput Analysis of Methylmalonic Acid in Serum, Plasma, and Urine: Method for Analyzing Isomers Without Chromatographic Separation

Kushnir

Nelson

Frank

et al. 2022

Clinical Applications of Mass Spectrometry in Biomolecular Analysis

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Highly sensitive and selective measurement of underivatized methylmalonic acid in serum and plasma by liquid chromatography-tandem mass spectrometry

Cited by 18 publications

References 20 publications

An LC-MS/MS method for serum methylmalonic acid suitable for monitoring vitamin B12 status in population surveys

An LC-MS/MS method for serum methylmalonic acid suitable for monitoring vitamin B12 status in population surveys

Development and validation of a simple HPLC‐MS/MS method for the quantification of methylmalonic acid in human serum without a derivatization step

LC–MS/MS Method for High-Throughput Analysis of Methylmalonic Acid in Serum, Plasma, and Urine: Method for Analyzing Isomers Without Chromatographic Separation

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