Development of a validated UPLC-MS/MS method for PK/PD analysis of SYL930 and its two major metabolites in dogs

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• 作者：Manman Zhao ; Jiaqi Mi ; Xin Liu ; Yan Wang ; Xiangmeng Wu ; Jinping Hu and Yan Li
• 刊名：Biomedical Chromatography
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：31
• 期：2
• 全文大小：884K
• ISSN：1099-0801

文摘

A sensitive and specific UPLC-MS/MS method was developed and validated for the simultaneous determination of 2-amino-2-(2-(4′-(2-propyloxazol-4-yl)-[1,1′-biphenyl]-4-yl)ethyl)propane-1,3-diol (SYL930), phosphorylated metabolite (SYL930-P) and hydroxylated metabolite (SYL930-M) in dog blood using SYL927 and SYL927-P, analogues of SYL930, as the internal standards. Analytes were extracted with protein precipitation followed by chromatographic separation on a ZorbaxSB-C₁₈ column (3.5 μm, 2.1 × 100 mm) with a gradient elution of methanol–water containing 0.1% formic acid (v/v). A triple quadrupole tandem mass spectrometer operating in the positive electrospray ionization mode was used to detect SYL930, SYL930-P, SYL930-M and IS transitions of 381.2 → 364.2, 461.2 → 334.2, 397.3 → 380.3, 367.1 → 350.4 and 447.5 → 320.2, respectively. The linear calibration curves for SYL930, SYL930-P and SYL930-M were 0.5–500, 0.2–100 and 0.5–100 ng/mL, respectively (r² > 0.99). The intra-day and inter-day precisions (RSD, %) of analytes did not exceed 9.16% except for low QCs (≤16.22%), and the accuracy (RE, %) ranged from −14 to 11.4%. The mean recoveries for SYL930, SYL930-P and SYL930-M in dog blood were 85.13–107.94, 73.84–80.08 and 85.64–95.44%, respectively. The validated method was successfully applied to pharmacokinetic and PK/PD studies of SYL930 and its two major metabolites in dogs after an oral administration of SYL930.