The First Affiliated Hospital of Wenzhou Medical University, 325000 Wenzhou, PR China.
The First Affiliated Hospital of Wenzhou Medical University, 325000 Wenzhou, PR China.
J Pharm Biomed Anal. 2020 Aug 5;187:113355. doi: 10.1016/j.jpba.2020.113355. Epub 2020 May 11.
Duvelisib, a new oral phosphoinositide-3-kinase (PI3K)-δ and PI3K-γ inhibitor, was recently approved in the USA as the therapeutic drug for patients with the diseases of relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). In the present study of our research, a quick and simple bioanalytical method based on ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) technique was fully explored and established for the quantification of plasma duvelisib concentrations from beagle dog in which gilteritinib was used as the internal standard (IS). After a simple and quick protein precipitation treated with acetonitrile, the chromatographic separation of the analyte was carried out on an Acquity BEH C18 column (2.1 mm × 50 mm, 1.7 μm) conducted in a gradient elution procedure where acetonitrile (solvent A) and 0.1 % formic acid in water (solvent B) consisted as the mobile phase. The measurements of the analyte and IS were explored using a XEVO TQS triple quadrupole tandem mass spectrometer, which was comprised with electrospray ionization (ESI) source in positive ion mode. Selected reaction monitoring (SRM) mode was employed to detect the parent-to-daughter ion transitions as follows: m/z 416.88 → 281.88 for duvelisib, and m/z 553.09 → 436.01 for IS, respectively. The assay was successfully established in the calibration range from 0.5 to 3000 ng/mL for duvelisib, where the lower limit of quantification (LLOQ) was set at 0.5 ng/mL. The precisions of intra-day and inter-day for duvelisib were all below 12.6 %, and the accuracies were from -2.5% to 14.1%. Both matrix effect and mean recovery of the analyte and IS were all acceptable, and the analyte was stable during the assay and storage in dog plasma samples. The novel established bioanalytical method based on UPLC-MS/MS technique was effectively employed to the investigation of the pharmacokinetic profile of duvelisib in beagle dogs following a 1.34 mg/kg single dose of oral administration.
杜韦利昔布（Duvelisib）是一种新型的口服磷酸肌醇 3-激酶（PI3K）-δ 和 PI3K-γ 抑制剂，最近在美国被批准用于治疗复发性或难治性慢性淋巴细胞白血病（CLL）和小淋巴细胞淋巴瘤（SLL）患者的治疗药物。在本研究中，我们充分探索并建立了一种快速简便的基于超高效液相色谱串联质谱（UPLC-MS/MS）技术的生物分析方法，用于定量检测贝格尔犬血浆中的杜韦利昔布浓度，其中吉尔替尼（gilteritinib）作为内标（IS）。经过简单快速的乙腈蛋白沉淀处理后，采用 Acquity BEH C18 柱（2.1mm×50mm，1.7μm）在梯度洗脱程序中进行色谱分离，流动相由乙腈（溶剂 A）和 0.1%甲酸水溶液（溶剂 B）组成。采用 XEVO TQS 三重四极杆串联质谱仪进行分析物和 IS 的测量，该质谱仪采用正离子模式的电喷雾电离（ESI）源。采用选择反应监测（SRM）模式检测母离子-子离子跃迁，如下所示：m/z 416.88→281.88 用于杜韦利昔布，m/z 553.09→436.01 用于 IS。该方法在杜韦利昔布的校准范围为 0.5 至 3000ng/mL 时成功建立，定量下限（LLOQ）设定为 0.5ng/mL。杜韦利昔布的日内和日间精密度均低于 12.6%，准确度在-2.5%至 14.1%之间。分析物和 IS 的基质效应和平均回收率均在可接受范围内，并且在犬血浆样品的分析和储存过程中，分析物稳定。该方法成功应用于犬单次口服 1.34mg/kg 杜韦利昔布后的药代动力学研究。
