Challenges for Detecting Valproic Acid in a Nontargeted Urine Drug Screening Method

Jeffrey D. Pope, Marion J. Black, Olaf H. Drummer, Hans G. Schneider

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3 Citations (Scopus)


Background: Valproic acid (VPA) is a widely prescribed medicine, and acute toxicity is possible. As such, it should be included in any nontargeted urine drug screening method. In many published liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS) methods, VPA is usually measured using a pseudo-multiple reaction monitoring (MRM) transition. We investigate a simple ultra-high-performance liquid chromatography-quadrupole time-of-flight (QTof) approach to detect the presence of VPA with more confidence. Methods: Three commercially sourced VPA metabolites were characterized and added to a nontargeted high-resolution MS urine drug screening method. All analyses were performed on a Waters Xevo G2-XS LC-QTof in negative electrospray ionization mode. The mass detector was operated in MS E mode, and data were processed with UNIFI software. Sixty-eight patient urine samples, which were previously identified by a well-established gas chromatography-MS method as containing VPA, were analyzed on the Waters Xevo G2-XS LC-QTof, to validate this approach. Results: VPA metabolite standards were characterized, and their detection data were added to the broad drug screening library. VPA metabolites were readily detectable in the urine of patients taking VPA. Conclusions: The inclusion of characterized VPA metabolites provides a simple and reliable method enabling the detection of VPA in nontargeted urine drug screening.

Original languageEnglish
Pages (from-to)457-460
Number of pages4
JournalTherapeutic Drug Monitoring
Issue number4
Publication statusPublished - 1 Aug 2017


  • high-resolution mass spectrometry
  • time-of-flight
  • urine drug screen
  • valproic acid

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