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

Pope, Jeffrey D.; Black, Melvin B.; Drummer, Olaf H.; Schneider, Hans‐Gerhard

doi:10.1097/ftd.0000000000000417

Cited by 8 publications

(7 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The methanolic extracts of the pills were analyzed by the same nontargeted and validated UHPLC-QTof method that is used routinely for urine drug screens (2). No positive identifications were made; however, 2 unknown peaks were identified on the total-ion chromatogram.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Novel Benzodiazepines (Clonazolam and Flubromazolam) Identified in Candy-Like Pills

Pope

Choy

Drummer

et al. 2018

The Journal of Applied Laboratory Medicine

View full text Add to dashboard Cite

Objectives To identify the contents of pills found on an intoxicated patient by ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTof).5 To highlight the potential ability that this technique can add to the clinical laboratory. Methods Illicit PEZ-like pills purchased from an online vendor, containing unknown substances, were investigated by UHPLC-QTof. Accurate mass and experimental data were obtained. Tentative identifications were subsequently confirmed with commercial standards. Results Accurate mass data, high-energy mass spectra, elucidation software, and a review of the scientific literature enabled the tentative identification of clonazolam and flubromazolam in the PEZ-like pills. On the basis of these tentative identifications, commercial standards were purchased to confirm the initial findings. On subsequent reinterrogation of the data, flubromazolam was identified in the urine specimen of the patient. Conclusions Utilizing high-resolution mass data, 2 novel benzodiazepines were tentatively identified by reinterrogation of a routine analysis for drugs of abuse. Use of UHPLC-QTof in a clinical toxicology laboratory provides additional capabilities to explain and potentially improve treatment of patients presenting to the emergency department with symptoms possibly due to toxic substance ingestion.

show abstract

Section: Resultsmentioning

confidence: 99%

“…The UHPLC-QTof analyses were performed as 2 separate methods, 1 operated in positive electrospray ionization (ESI) mode and 1 in negative ESI mode. Exhaustive method details of UHPLC-QTof are described elsewhere (1,2). Briefly, a 15-min gradient elution (0.4 mL/min) was used for ESI+ mode.…”

Section: Methodsmentioning

confidence: 99%

Novel Benzodiazepines (Clonazolam and Flubromazolam) Identified in Candy-Like Pills

Pope

Choy

Drummer

et al. 2018

The Journal of Applied Laboratory Medicine

View full text Add to dashboard Cite

show abstract

“…[6][7][8][9][10] Another type of data analysis is metabolomics, where multivariate data analysis is used to elucidate differences between sample groups, i.e., positive versus negative controls. 14,15 The therapeutic range of VPA in plasma is 50-100 mg/L. 13 Valproate (valproic acid; VPA) is a fatty acid and frequently used anti-epileptic drug, and is therefore generally included in STA in forensic toxicology.…”

Section: Introductionmentioning

confidence: 99%

“…13 Valproate (valproic acid; VPA) is a fatty acid and frequently used anti-epileptic drug, and is therefore generally included in STA in forensic toxicology. 14,15,[17][18][19] Metabolites of VPA have been used for confirmation, 14,17,18 and adducts of VPA with common mobile phase additives enable use of real mass transitions with increased sensitivity. 16 Analysis of VPA using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and LC-HRMS is often performed in negative electrospray ionization mode (ESI − ) with pseudo-multiplereaction monitoring (MRM) transition of mass-to-charge (m/z) 143 → 143, corresponding to the [M-H] − precursor.…”

Section: Introductionmentioning

confidence: 99%

“…16 Analysis of VPA using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and LC-HRMS is often performed in negative electrospray ionization mode (ESI − ) with pseudo-multiplereaction monitoring (MRM) transition of mass-to-charge (m/z) 143 → 143, corresponding to the [M-H] − precursor. 14,15,[17][18][19] Metabolites of VPA have been used for confirmation, 14,17,18 and adducts of VPA with common mobile phase additives enable use of real mass transitions with increased sensitivity. 20 However, LC-HRMS screening in toxicology is often performed solely using positive electrospray ionization (ESI + ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Retrospective analysis for valproate screening targets with liquid chromatography–high resolution mass spectrometry with positive electrospray ionization: An omics‐based approach

Mollerup

Rasmussen

Johansen

et al. 2018

Drug Testing and Analysis

View full text Add to dashboard Cite

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. KEYWORDS biomarker, forensic toxicology screening, indirect screening, retrospective analysis, untargeted high-resolution mass spectrometry screening

show abstract

A review of recent advances in microsampling techniques of biological fluids for therapeutic drug monitoring

Tey

See

2021

Journal of Chromatography A

View full text Add to dashboard Cite

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

Abstract: The inclusion of characterized VPA metabolites provides a simple and reliable method enabling the detection of VPA in nontargeted urine drug screening.

Cited by 8 publications

References 11 publications

Novel Benzodiazepines (Clonazolam and Flubromazolam) Identified in Candy-Like Pills

Novel Benzodiazepines (Clonazolam and Flubromazolam) Identified in Candy-Like Pills

Retrospective analysis for valproate screening targets with liquid chromatography–high resolution mass spectrometry with positive electrospray ionization: An omics‐based approach

A review of recent advances in microsampling techniques of biological fluids for therapeutic drug monitoring

Contact Info

Product

Resources

About