Department of Biochemistry and the Cancer Centre for Children, The Children's Hospital at Westmead, Westmead, Australia.
Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, Australia.
J Sep Sci. 2022 Jul;45(14):2508-2519. doi: 10.1002/jssc.202101013. Epub 2022 May 20.
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 H O 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 (R > 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.
建立并验证了一种采用体积排代微采样装置，在 10 μL 全血中同时定量检测长春新碱和曲贝替定的液相色谱-串联质谱法。从装置中提取样品，用人血浆基质中的校准品进行定量分析。采用 Shimpack XR ODS III C18 固定相和 H 2 O-甲醇流动相溶剂（含 0.1%甲酸），梯度洗脱，流速为 0.2 mL/min，洗脱 6.0 min，实现了长春新碱和曲贝替定的分离。该方法在 1200 ng/mL 内呈线性（两个分析物的 R 值均大于 0.99），校准品准确度在名义浓度的 ±15%范围内，长春新碱和曲贝替定的分析物变异系数均小于 15%。该方法成功应用于单药和联合治疗 24 h 的小鼠药代动力学评估，与曲贝替定联合应用时长春新碱药物暴露增加了 2.3 倍。本研究验证了该方法在动物研究中用于药物暴露的纵向分析的适用性。
