Quantification of vincristine and tariquidar by liquid chromatography‐tandem mass spectrometry in mouse whole blood using volumetric absorptive microsampling for pharmacokinetic applications

Abstract

A liquid chromatography‐tandem mass spectrometry method was developed and validated for the simultaneous quantification of vincristine and tariquidar in 10 μL of mouse whole blood using volumetric absorptive microsampling devices. Samples were extracted from the devices and quantified against calibrators prepared in a human blood plasma matrix. Separation of vincristine and tariquidar was achieved using a Shimpack XR ODS III C18 stationary phase and H2O and methanol mobile phase solvents containing 0.1% formic acid, running a gradient elution at a flow rate of 0.2 mL/min over 6.0 min. The method was linear up to 1200 ng/mL (R2 > 0.99 for both analytes), with calibrator accuracy within ± 15% of the nominal concentrations and analyte coefficient of variance <15% for both vincristine and tariquidar. Pharmacokinetic assessment of both analytes was successfully applied in mice as both single‐agent therapy and combination therapy over a 24‐h period, and a 2.3‐fold increase in vincristine drug exposure was observed in combination with tariquidar. This study validates the use of this approach for longitudinal analysis of drug exposure in animal studies.

Blood microsampling technologies: Innovations and applications in 2022

“…In the work of Rosser et al., the PK assessment of vincristine and tariquidar in mice using an LC‐MS/MS approach was effectively carried out using the VAMS technology. Assessment of both single‐agent therapy and combination therapy over a 24 h period in 10 µL microsamples revealed a 2.3‐fold increase in vincristine drug exposure when combined with tariquidar, which validated the use of the approach for longitudinal analysis of drug exposure in animal studies 27 . Xu et al.…”

“…90 Guidelines that consolidate the regulatory perspectives on microsampling and support its use in blood sampling have also been added to and reviewed by the which validated the use of the approach for longitudinal analysis of drug exposure in animal studies. 27 Xu et al evaluated the feasibility of CMS coupled to HPLC-MS/MS for mice PK studies using transresveratrol as the model drug. The PK parameters of the drug and its associated metabolites found in the study were comparable with those reported in previous studies, which demonstrated that CMS provides credible samples for subsequent quantitative PK analysis.…”

“… 20 Furthermore, paper‐based ionization techniques such as paper spray ionization (PSI) for MS have enabled the direct analysis of a broad spectrum of analytes in dried microsamples without the requirement of any prior sample pretreatment. 21 These sophisticated approaches have driven the implementation of microsampling in various biomedical domains; newborn and metabolic screening, 22 , 23 biomarker research, 21 , 24 , 25 pharmacokinetic (PK) and pharmacodynamic (PD) studies, 26 , 27 therapeutic drug monitoring (TDM), 28 , 29 , 30 , 31 , 32 , 33 forensic toxicology, 34 , 35 , 36 sports anti‐doping, 37 , 38 , 39 metabolomics 22 , 40 , 41 and proteomics. 24 , 42 , 43 Since 70% of medical decisions are governed by diagnostic blood tests, 44 several medical technology companies are investing in the development of innovative at‐home blood microsampling devices to make blood work more accessible and convenient.…”

Multidrug Resistance of Cancer Cells and the Vital Role of P-Glycoprotein

“…They have no pharmacological interactions with chemotherapeutic drugs and have been discovered to be 200 times more powerful than the previous two generations of inhibitors. Zosuquidar (LY335979), mitotane (NSC-38721), laniquidar (R101933) [71], tariquidar (XR9576) [72], ONT-093, elacridar (F12091), annamycin, HM30181, R10933, and biricodar are other examples [73]. According to the 3D QSAR and QSAR activity, the structure of the inhibitors is mostly responsible for producing the inhibitory activities.…”

“…Furthermore, the expression of the T-cell exhaustion markers PD-1 and CTLA-4 was reduced in this subset of CD4+helper-T cells. It has been demonstrated that Th17 and Th1 CD4+T-helper cell subsets secrete anti-tumour inflammatory cytotoxic cy-tokines such as IL-17, IFNg, TNFa, and granzyme [72,104,105]. P-gp-expressing CD4+T cells (CD4+CD73+T cells) were found to secrete more anti-cancer cytokines in tumourinfiltrating breast and ovarian carcinomas.…”