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Retrospective analysis for valproate screening targets with liquid chromatography–high resolution mass spectrometry with positive electrospray ionization: An omics‐based approach
Author(s) -
Mollerup Christian Brinch,
Rasmussen Brian Schou,
Johansen Sys Stybe,
Mardal Marie,
Linnet Kristian,
Dalsgaard Petur Weihe
Publication year - 2019
Publication title -
drug testing and analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 54
eISSN - 1942-7611
pISSN - 1942-7603
DOI - 10.1002/dta.2543
Subject(s) - electrospray ionization , chemistry , chromatography , mass spectrometry , electrospray , valproic acid , medicine , epilepsy , psychiatry
Liquid chromatography coupled with high‐resolution mass spectrometry (LC–HRMS) is an important analytical tool in the systematic toxicological analysis performed in forensic toxicology. However, some important compounds, such as the antiepileptic drug valproate (valproic acid; VPA), cannot be directly detected with positive electrospray ionization (ESI + ) due to poor ionization. Here we demonstrate an omics‐based retrospective analysis for the identification of indirect screening targets for VPA in whole blood with LC–ESI + –HRMS. Analysis was performed utilizing data acquired across four years from LC–ESI + –HRMS, with VPA results from a quantitative LC–MS/MS method. The combined data with VPA results were split into an exploration set ( n = 68; 28% positive) and a test set ( n = 37; 32% positive). Eight indirect targets for VPA were identified in the exploration set. The evaluation of these targets was confirmed with retrospective target analysis of the test set. Using a combination of two out of the eight indirect targets, we attained a sensitivity of 92% ( n = 12; VPA concentration range: 4.4–29.7 mg/kg) and 100% specificity ( n = 25) for VPA with LC–ESI + –HRMS. VPA screening targets were identified with retrospective data analysis and could be appended to the existing screening procedure. A sensitive and specific screening with LC–ESI + –HRMS was achieved with targets corresponding to the sodium adducts of C 7 H 14 O 3 and C 8 H 14 O 3 . Three chromatographic resolved isomer peaks were observed for the latter, and the consistently most intense peak was tentatively identified as 3‐hydroxy‐4‐en‐VPA.