Development and validation of an LC-MS/MS method for the determination of a novel thienoquinolin urea transporter inhibitor PU-48 in rat plasma and its application to a pharmacokinetic study.
Development and validation of an LC-MS/MS method for the determination of a novel thienoquinolin urea transporter inhibitor PU-48 in rat plasma and its application to a pharmacokinetic study.
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晶态和自纳米乳化给药系统（SNEDDS）对新型抗 HIV 化合物 6-benzyl-1-benzyloxymethyl-5-iodouracil 大鼠口服生物利用度的影响。
DOI：
10.1002/bmc.4157
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Guo-Liang Zhang
中科院分区：
文献类型：
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作者：
Zhi-Yuan Zhang;Xin Wang;Dan Liu;Hua Zhang;Qiang Zhang;Ying-Yuan Lu;Pu Li;Bao-Xue Yang;Ya-Qing Lou;Chuang Lu;Ya-Xin Lou;Guo-Liang Zhang
建立了一种新的利尿剂硫代喹啉尿素转运体抑制剂3-氨基-6-甲氧基硫代[2，3-b]喹诺酮-2-羧酸甲酯(PU-48)的高效液相色谱-串联质谱(LC-MS/MS)测定方法。采用反相C18色谱柱(10 0×2.1 mm，3μm)，流动相为乙腈-水加0.0 5%甲酸，梯度洗脱，流速为0.3m L/m in。样品检测采用电喷雾电离源正向多反应监测模式的三四极串联质谱计。保留时间PU-48为6.2min，甲地孕酮为7.2min(内标)。监测到的离子跃迁为PU-48的质量电荷比(m/z)289.1→229.2和内标的m/z 385.3→267.1。PU-48的线性范围为0.1-1000 ng/m L(R2>；0.99)，定量下限为0.1 ng/m L。充分验证了该方法的精密度、准确度和稳定性。该方法已成功地应用于PU-48在大鼠体内的药动学研究。
A specific, sensitive and stable high‐performance liquid chromatographic–tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantitative determination of methyl 3-amino-6-methoxythieno [2,3-b]quinolone-2-carboxylate (PU-48), a novel diuretic thienoquinolin urea transporter inhibitor in rat plasma. In this method, the chromatographic separation of PU-48 was achieved with a reversed‐phase C18 column (100 × 2.1 mm, 3 μm) at 35°C. The mobile phase consisted of acetonitrile and water with 0.05% formic acid added with a gradient elution at flow rate of 0.3 mL/min. Samples were detected with the triple-quadrupole tandem mass spectrometer with multiple reaction monitoring mode via electrospray ionization source in positive mode. The retention time were 6.2 min for PU-48 and 7.2 min for megestrol acetate (internal standard, IS). The monitored ion transitions were mass‐to‐charge ratio (m/z) 289.1 → 229.2 for PU‐48 and m/z 385.3 → 267.1 for the internal standard. The calibration curve for PU‐48 was linear over the concentration range of 0.1–1000 ng/mL (r2 > 0.99), and the lower limit of quantitation was 0.1 ng/mL. The precision, accuracy and stability of the method were validated adequately. The developed and validated method was successfully applied to the pharmacokinetic study of PU-48 in rats.