Department of Pharmaceutical Chemistry and Drug Bioavailability Unit, Central Laboratory, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
National Organization for Drug Control and Research, Cairo 12611, Egypt.
Molecules. 2020 Mar 31;25(7):1600. doi: 10.3390/molecules25071600.
Baricitinib, is a selective and reversible Janus kinase inhibitor, is commonly used to treat adult patients with moderately to severely active rheumatoid arthritis (RA). A fast, reproducible and sensitive method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the quantification of baricitinib in rat plasma has been developed. Irbersartan was used as the internal standard (IS). Baracitinib and IS were extracted from plasma by liquid-liquid extraction using a mixture of n-hexane and dichloromethane (1:1) as extracting agent. Chromatographic separation was performed using Acquity UPLC HILIC BEH 1.7 µm 2.1 × 50 mm column with the mobile phase consisting of 0.1% formic acid in acetonitrile and 20 mM ammonium acetate (pH 3) (97:3). The electrospray ionization in the positive-mode was used for sample ionization in the multiple reaction monitoring mode. Baricitinib and the IS were quantified using precursor-to-production transitions of / 372.15 > 251.24 and 429.69 > 207.35 for baricitinib and IS, respectively. The method was validated according to the recent FDA and EMA guidelines for bioanalytical method validation. The lower limit of quantification was 0.2 ng/mL, whereas the intra-day and inter-day accuracies of quality control (QCs) samples were ranged between 85.31% to 89.97% and 87.50% to 88.33%, respectively. Linearity, recovery, precision, and stability parameters were found to be within the acceptable range. The method was applied successfully applied in pilot pharmacokinetic studies.
巴利昔替尼是一种选择性和可逆的 Janus 激酶抑制剂，通常用于治疗成人中至重度活跃型类风湿关节炎（RA）。已经开发出一种快速、重现性和灵敏的液相色谱-串联质谱（LC-MS/MS）方法，用于定量大鼠血浆中的巴利昔替尼。依贝沙坦被用作内标（IS）。巴利昔替尼和 IS 通过使用正己烷和二氯甲烷（1:1）混合物作为提取剂的液-液萃取从血浆中提取。采用 Acquity UPLC HILIC BEH 1.7 µm 2.1 × 50 mm 柱进行色谱分离，流动相由乙腈中的 0.1%甲酸和 20 mM 乙酸铵（pH 3）（97:3）组成。在正离子模式下进行电喷雾电离，采用多反应监测模式进行样品离子化。巴利昔替尼和 IS 分别采用 / 372.15 > 251.24 和 429.69 > 207.35 的前体产物过渡进行定量。该方法按照最近 FDA 和 EMA 的生物分析方法验证指南进行了验证。定量下限为 0.2 ng/mL，而 QC 样品的日内和日间准确度在 85.31%至 89.97%和 87.50%至 88.33%之间。线性、回收率、精密度和稳定性参数均在可接受范围内。该方法已成功应用于初步药代动力学研究。
