Overcoming interference with the detection of a stable isotopically labeled microtracer in the evaluation of beclabuvir absolute bioavailability using a concomitant microtracer approach

Jiang, Hao; Titsch, Craig; Zeng, Jianing; Jones, Barry R; Joyce, P L; Gandhi, Yash; Turley, Wesley A.; Burrell, Richard C.; Aubry, Anne; Arnold, Mark E.

doi:10.1016/j.jpba.2017.04.030

Cited by 7 publications

(4 citation statements)

References 26 publications

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“…Targeted metabolite quantitation in PRM has been described in parallel of untargeted metabolomics (25). Studies in PRM mode have also been reported for the quantitation of drugs such as anticancer (abiraterone) (26) and antiviral drug for the treatment of hepatitis C (beclabuvir) in plasma (27). Anticoagulant rodenticides (28) and sterols quantitation (29) have also been performed using this analytical strategy.…”

Section: Introductionmentioning

confidence: 99%

Parallel Reaction Monitoring-Based Quantification of Cannabinoids in Whole Blood

Joye

Widmer

Favrat

et al. 2020

Journal of Analytical Toxicology

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Cannabis is the most consumed drug of abuse, making it the primary target for identification and quantification in human whole blood regarding forensic and clinical toxicology analyses. Among biological matrices, blood is the reference for toxicological interpretation. A highly sensitive and selective liquid chromatography (LC) hyphenated with high-resolution mass spectrometry (HRMS) was developed for the quantification of Δ9-tetrahydrocannabinol (THC), 11-hydroxytetrahydrocannabinol (THC-OH), 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH) and cannabidiol (CBD). Those cannabinoids were extracted from 1 mL of whole blood by a simple liquid–liquid extraction (LLE) in acidic conditions. HRMS was performed on an Orbitrap-based instrument using its trapping capabilities and increased selectivity for parallel reaction monitoring (PRM) quantification in positive polarity with a negative polarity switching for THC-OH and THC-COOH. Although selected reaction monitoring (SRM) and PRM-targeted methods have similar performance in terms of linearity, dynamic range, precision and repeatability, Orbitrap-based PRM provides a higher specificity due to the use of high-resolution mode separating background ions from the targeted molecules. The method was fully validated according to guidelines set forth by the “Société Française des Sciences et des Techniques Pharmaceutiques” (SFSTP). Trueness was measured below 107% for all tested concentrations. Repeatability and intermediate precision were found to be lower than 12% while the assay was found to be linear in the concentration range of 0.4–20 ng/mL for THC, THC-OH and CBD and of 2–100 ng/mL for THC-COOH. Recovery (RE) and matrix effect (ME) ranged from 70.6 to 102.5% and from −40 to 6.6%, respectively. The validated method provides an efficient procedure for the simultaneous and rapid quantification of cannabinoids in PRM mode providing an alternative over classical SRM.

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Section: Introductionmentioning

confidence: 99%

Parallel Reaction Monitoring-Based Quantification of Cannabinoids in Whole Blood

Joye

Widmer

Favrat

et al. 2020

Journal of Analytical Toxicology

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“…administration, without the need for 14 C-drug and the consequential support by AMS. [19][20][21][22] By its very nature, as a stable (non-radiolabel) isotope, the use of 13 C as the tracer negates any considerations around shipment, storage, and handling of samples with respect to those that have to be considered for source materials and samples containing radioactivity, albeit that in some territories there may be a cutoff below which samples are considered to be non-radioactive even when they contain measurable levels of radioactivity above the natural background.…”

Section: A Note On Data Deconvolutionmentioning

confidence: 99%

“…This design has found favor in situations where the focus of the investigation is to establish the PKs of the drug following i.v. administration, without the need for 14 C‐drug and the consequential support by AMS 19–22 …”

Section: A Note On Data Deconvolutionmentioning

confidence: 99%

Non‐Labeled, Stable Labeled, or Radiolabelled Approaches for Provision of Intravenous Pharmacokinetics in Humans: A Discussion Piece

Young,

Spracklin,

James

et al. 2023

Clin Pharma and Therapeutics

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A review of the use of microdoses and isotopic microtracers for clinical intravenous pharmacokinetic (i.v. PK) data provision is presented. The extent of application of the varied approaches available and the relative merits of each are highlighted with the aim of assisting practitioners in making informed decisions on the most scientifically appropriate design to adopt for any given new drug in development. It is envisaged that significant efficiencies will be realized as i.v. PK data in humans becomes more routinely available for suitable assets in early development, than has been the case prior to the last decade.

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“…Even though this strategy is relatively recent regarding illicit drug and pharmaceuticals analyses in toxicology, it has received a growing interest. Indeed, PRM quantification has been reported for the quantitative analysis of abiraterone (Bhatnagar et al, 2018), beclabuvir (Jiang et al, 2017), anticoagulant rodenticides (Gao et al, 2018), and sterols (Schott et al, 2018). Regarding drugs of abuse, a first application has been described for the quantification of cannabinoids in whole blood (Joye et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Driving Under the Influence of Drugs: A Single Parallel Monitoring-Based Quantification Approach on Whole Blood

et al. 2020

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Driving under the influence of psychoactive substances is a major cause of motor vehicle crashes. The identification and quantification of substances most frequently involved in impaired-driving cases in a single analytic procedure could be an important asset in forensic toxicology. In this study, a highly sensitive and selective liquid chromatography (LC) approach hyphenated with Orbitrap high-resolution mass spectrometry (HRMS) was developed for the quantification of the main drugs present in the context of driving under the influence of drugs (DUID) using 100 µL of whole blood. This procedure involves a simple sample preparation and benefit from the selectivity brought by parallel reaction monitoring (PRM) allowing to solve most DUID cases using a single multi-analyte injection. The method was fully validated for the quantification of the major classes of psychoactive substances associated with impaired-driving (cannabinoids, cocaine and its metabolites, amphetamines, opiates and opioids, and the major benzodiazepines and z-drugs). The validation guidelines set by the "Société Française des Sciences et des Techniques Pharmaceutiques" (SFSTP) were respected for 22 psychoactive substances using 15 internal standards. Trueness was measured to be between 95.3 and 107.6% for all the tested concentrations. Precision represented by repeatability and intermediate precision was lower than 12% while recovery (RE) and matrix effect (ME) ranged from 49 to 105% and from −51 to 3%, respectively. The validated procedure provides an efficient approach for the simultaneous and simple quantification of the major drugs associated with impaired driving benefiting from the selectivity of PRM.

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Overcoming interference with the detection of a stable isotopically labeled microtracer in the evaluation of beclabuvir absolute bioavailability using a concomitant microtracer approach

Cited by 7 publications

References 26 publications

Parallel Reaction Monitoring-Based Quantification of Cannabinoids in Whole Blood

Parallel Reaction Monitoring-Based Quantification of Cannabinoids in Whole Blood

Non‐Labeled, Stable Labeled, or Radiolabelled Approaches for Provision of Intravenous Pharmacokinetics in Humans: A Discussion Piece

Driving Under the Influence of Drugs: A Single Parallel Monitoring-Based Quantification Approach on Whole Blood

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