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Multiplexed LC-MS/MS analysis of methylsuccinic acid, ethylmalonic acid, and glutaric acid in plasma and urine.
Peng, Kuan-Wei; Klotz, Allison; Guven, Arcan; Gray, Kayleigh; Friss, Tracey; Ravipaty, Shobha; Sarangarajan, Rangaprasad; Tolstikov, Vladimir; Kellogg, Mark D; Narain, Niven R; Kiebish, Michael A.
  • Peng KW; BERG, 500 Old Connecticut Path, Framingham, MA, 01701, USA.
  • Klotz A; BERG, 500 Old Connecticut Path, Framingham, MA, 01701, USA.
  • Guven A; BERG, 500 Old Connecticut Path, Framingham, MA, 01701, USA.
  • Gray K; BERG, 500 Old Connecticut Path, Framingham, MA, 01701, USA.
  • Friss T; BERG, 500 Old Connecticut Path, Framingham, MA, 01701, USA.
  • Ravipaty S; BERG, 500 Old Connecticut Path, Framingham, MA, 01701, USA.
  • Sarangarajan R; BERG, 500 Old Connecticut Path, Framingham, MA, 01701, USA.
  • Tolstikov V; BERG, 500 Old Connecticut Path, Framingham, MA, 01701, USA.
  • Kellogg MD; BERG, 500 Old Connecticut Path, Framingham, MA, 01701, USA; Department of Pathology, Harvard Medical School, Boston, MA, USA; Department of Laboratory Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
  • Narain NR; BERG, 500 Old Connecticut Path, Framingham, MA, 01701, USA.
  • Kiebish MA; BERG, 500 Old Connecticut Path, Framingham, MA, 01701, USA. Electronic address: michael.kiebish@berghealth.com.
Anal Biochem ; 645: 114604, 2022 05 15.
Article en En | MEDLINE | ID: mdl-35217005
ABSTRACT
Low molecular-mass aliphatic carboxylic acids are critically important for intermediate metabolism and may serve as important biomarkers for metabolic homeostasis. Here in, we focused on multiplexed method development of aliphatic carboxylic analytes, including methylsuccinic acid (MSA), ethylmalonic acid (EMA), and glutaric acid (GA). Also assessed was their utility in a population's health as well as metabolic disease screening in both plasma and urine matrices. MSA, EMA, and GA are constitutional isomers of dicarboxylic acid with high polarity and poor ionization efficiency, resulting in such challenges as poor signal intensity and retention, particularly in reversed-phase liquid chromatography with electrospray mass spectrometry (RP-LC-ESI-MS/MS). Derivatization using n-butanol was performed in the sample preparation to enhance the signal intensity accompanied with a positive charge from ionization in complicated biomatrices as well as to improve the separation of these isomers with optimal retention. Fit-for-purpose method validation results demonstrated quantitative ranges for MSA/EMA/GA from 5/10/20 ng/mL to 400 ng/mL in plasma analysis, and 100/200/100 ng/mL to 5000/10000/5000 ng/mL in urine analysis. This validated method demonstrates future utility when exploring population health analysis and biomarker development in metabolic diseases.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Espectrometría de Masa por Ionización de Electrospray / Espectrometría de Masas en Tándem Idioma: En Año: 2022 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Espectrometría de Masa por Ionización de Electrospray / Espectrometría de Masas en Tándem Idioma: En Año: 2022 Tipo del documento: Article