ArticleJournal of pharmaceutical and biomedical analysis2021
Development and validation of an LC-MS/MS generic assay platform for small molecule drug bioanalysis.
Article in Journal of pharmaceutical and biomedical analysis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Resolution and Quantitation of Ribonucleosides and Deoxyribonucleosides in Digested Genomic DNA by UHPLC-MS/MS.Biomedical chromatography : BMC · 2026Article
- Dynamic Switching of Apoptosis-Modulating Bim Heterodimers in Response to BH3 Mimetics in Xenograft Models of Hematologic Malignancies.Molecular cancer therapeutics · 2026Article
- Murine toxicology and pharmacokinetics of lead next generation galeterone analog, VNPP433-3β.Steroids · 2023Article
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Authors and funding
6 authors.
Funding
Abstract
aimWe developed a generic high-performance liquid chromatography mass spectrometry approach for quantitation of small molecule compounds without availability of isotopically labelled standard.
methodsThe assay utilized 50 μL of plasma and offers 8 potential internal standards (IS): acetaminophen, veliparib, busulfan, neratinib, erlotinib, abiraterone, bicalutamide, and paclitaxel. Preparation consisted of acetonitrile protein precipitation and aqueous dilution in a 96 well-plate format. Chromatographic separation was achieved with a Kinetex C18 reverse phase (2.6 μm, 2 mm x 50 mm) column and a gradient of 0.1 % formic acid in acetonitrile and water over an 8 min run time. Mass spectrometric detection was performed on an AB SCIEX4000QTRAP with electrospray, positive-mode ionization. Performance of the generic approach was evaluated with seven drugs (LMP744, olaparib, cabozantinib, triapine, ixabepilone, berzosertib, eribulin) for which validated assays were available.
resultsThe 8 IS covered a range of polarity, size, and ionization; eluted over the range of chromatographic retention times; were quantitatively extracted; and suffered limited matrix effects. The generic approach proved to be linear for test drugs evaluated over at least 3 orders of magnitude starting at 1-10 ng/mL, with extension of assay ranges with analyte isotopologue MRM channels. At a bias of less than 16 % and precision within 15 %, the assay performance was acceptable.
conclusionThe generic approach has become a useful tool to further define the pharmacology of drugs studied in our laboratory and may be utilized as described, or as starting point to develop drug-specific assays with more extensive performance characterization.
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