Center of Clinical Pharmacology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, Zhejiang, China.
J Clin Pharm Ther. 2021 Apr;46(2):333-342. doi: 10.1111/jcpt.13285. Epub 2020 Nov 17.
Febuxostat is a well-known drug for treating hyperuricemia and gout. The published methods for determination of febuxostat in human plasma might be unsuitable for high-throughput determination and widespread application. We need to develop a highly selective, sensitive and rapid liquid chromatography-tandem mass spectrometry method.
The chromatographic separation was achieved on a Hypersil Gold-C18 (2.1 mm × 100 mm, 1.9 μm) column with mobile phase A (Water containing 0.1% formic acid) and mobile phase B (acetonitrile containing 0.1% formic acid). Multiple reaction monitoring (MRM) mode was used for quantification using target ions at m/z 315.3 → m/z 271.3 for febuxostat and m/z 324.3 → m/z 280.3 for Febuxostat-d (IS). A backpropagation artificial neural network (BPANN) pharmacokinetic model was constructed by the data of bioequivalence study.
After the LC-MS/MS method validated, it was successfully applied to the bioequivalence study of 30 human volunteers under fed condition. The predicted concentrations generated by BPANN model had a high correlation coefficient with experimental values.
A sensitive LC-MS/MS method had been developed and validated for determination of febuxostat in healthy subjects under fed condition, and a BPANN model was developed that can be used to predict the plasma concentration of febuxostat.
非布司他是一种治疗高尿酸血症和痛风的知名药物。已发表的非布司他在人血浆中的测定方法可能不适合高通量测定和广泛应用。我们需要开发一种高选择性、高灵敏度和快速的液相色谱-串联质谱法。
采用 Hypersil Gold-C18（2.1mm×100mm，1.9μm）柱，以流动相 A（含 0.1%甲酸的水）和流动相 B（含 0.1%甲酸的乙腈）为流动相，实现色谱分离。采用多反应监测（MRM）模式，以 m/z 315.3→m/z 271.3（目标离子）为非布司他，m/z 324.3→m/z 280.3（IS）为 Febuxostat-d 进行定量。通过生物等效性研究的数据构建反向传播人工神经网络（BPANN）药代动力学模型。
在验证 LC-MS/MS 方法后，成功应用于 30 名健康志愿者在进食条件下的生物等效性研究。BPANN 模型预测的浓度与实验值具有很高的相关性。
已开发并验证了一种灵敏的 LC-MS/MS 方法，用于测定进食条件下健康受试者中非布司他的浓度，并建立了一个 BPANN 模型，可用于预测非布司他的血浆浓度。
