PMID- 26602128
OWN - NLM
STAT- MEDLINE
DCOM- 20160908
LR  - 20151125
IS  - 1940-6029 (Electronic)
IS  - 1064-3745 (Linking)
VI  - 1378
DP  - 2016
TI  - High-Throughput Analysis of Methylmalonic Acid in Serum, Plasma, and Urine by 
      LC-MS/MS. Method for Analyzing Isomers Without Chromatographic Separation.
PG  - 159-73
LID - 10.1007/978-1-4939-3182-8_18 [doi]
AB  - Measurement of methylmalonic acid (MMA) plays an important role in the diagnosis 
      of vitamin B12 deficiency. Vitamin B12 is an essential cofactor for the enzymatic 
      carbon rearrangement of methylmalonyl-CoA (MMA-CoA) to succinyl-CoA (SA-CoA), and 
      the lack of vitamin B12 leads to elevated concentrations of MMA. Presence of 
      succinic acid (SA) complicates the analysis because mass spectra of MMA and SA 
      are indistinguishable, when analyzed in negative ion mode and the peaks are 
      difficult to resolve chromatographically. We developed a method for the selective 
      analysis of MMA that exploits the significant difference in fragmentation 
      patterns of di-butyl derivatives of the isomers MMA and SA in a tandem mass 
      spectrometer when analyzed in positive ion mode. Tandem mass spectra of di-butyl 
      derivatives of MMA and SA are very distinct; this allows selective analysis of 
      MMA in the presence of SA. The instrumental analysis is performed using liquid 
      chromatography-tandem mass spectrometry (LC-MS/MS) in positive ion mode, which 
      is, in combination with selective extraction of acidic compounds, is highly 
      selective for organic acids with multiple carboxyl groups (dicarboxylic, 
      tricarboxylic, etc.). In this method organic acids with a single carboxyl group 
      are virtually undetectable in the mass spectrometer; the only organic acid, other 
      than MMA, that is detected by this method is its isomer, SA. Quantitative 
      measurement of MMA in this method is performed using a deconvolution algorithm, 
      which mathematically resolves the signal corresponding to MMA and does not 
      require chromatographic resolution of the MMA and SA peaks. Because of its high 
      selectivity, the method utilizes isocratic chromatographic separation; 
      reconditioning and re-equilibration of the chromatographic column between 
      injections is unnecessary. The above features of the method allow high-throughput 
      analysis of MMA with analysis cycle time of 1 min.
FAU - Kushnir, Mark M
AU  - Kushnir MM
AD  - ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, 500 
      Chipeta Way, Salt Lake City, UT, USA. kushnmm@aruplab.com.
AD  - Department of Pathology, University of Utah, Salt Lake City, UT, USA. 
      kushnmm@aruplab.com.
FAU - Nelson, Gordon J
AU  - Nelson GJ
AD  - ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, 500 
      Chipeta Way, Salt Lake City, UT, USA.
FAU - Frank, Elizabeth L
AU  - Frank EL
AD  - ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, 500 
      Chipeta Way, Salt Lake City, UT, USA.
AD  - Department of Pathology, University of Utah, Salt Lake City, UT, USA.
FAU - Rockwood, Alan L
AU  - Rockwood AL
AD  - ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, 500 
      Chipeta Way, Salt Lake City, UT, USA.
AD  - Department of Pathology, University of Utah, Salt Lake City, UT, USA.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Methods Mol Biol
JT  - Methods in molecular biology (Clifton, N.J.)
JID - 9214969
RN  - 8LL8S712J7 (Methylmalonic Acid)
RN  - AB6MNQ6J6L (Succinic Acid)
SB  - IM
MH  - Blood Chemical Analysis/*methods
MH  - Chromatography, High Pressure Liquid/*methods
MH  - Humans
MH  - Isomerism
MH  - Limit of Detection
MH  - Methylmalonic Acid/*blood/chemistry/*urine
MH  - Statistics as Topic
MH  - Succinic Acid/chemistry
MH  - Tandem Mass Spectrometry/*methods
MH  - Time Factors
MH  - Urinalysis/*methods
OTO - NOTNLM
OT  - Data analysis
OT  - Deconvolution
OT  - Derivatization
OT  - Isomers
OT  - Liquid chromatography
OT  - Methylmalonic acid
OT  - Succinic acid
OT  - Tandem mass spectrometry
EDAT- 2015/11/26 06:00
MHDA- 2016/09/09 06:00
CRDT- 2015/11/26 06:00
PHST- 2015/11/26 06:00 [entrez]
PHST- 2015/11/26 06:00 [pubmed]
PHST- 2016/09/09 06:00 [medline]
AID - 10.1007/978-1-4939-3182-8_18 [doi]
PST - ppublish
SO  - Methods Mol Biol. 2016;1378:159-73. doi: 10.1007/978-1-4939-3182-8_18.