Simultaneous determination of tapentadol and its carbamate prodrug in rat plasma by UPLC‐MS/MS and its application to a pharmacokinetic study
Simultaneous determination of tapentadol and its carbamate prodrug in rat plasma by UPLC‐MS/MS and its application to a pharmacokinetic study
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UPLC—MS/MS同时测定大鼠血浆中他喷他多及其氨基甲酸酯前药及其在药代动力学研究中的应用
DOI：
10.1002/bmc.4300
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发表时间：
2018
影响因子：
1.8
通讯作者：
Longshan Zhao
中科院分区：
文献类型：
--
作者：
Tianhong Zhang;Cuiru Liu;Yingchao Li;Rujie Yang;Shuqi Zhang;Longshan Zhao
合成了他喷他多的前药，即他喷他多氨基甲酸酯（WWJ 01），以提高他喷他多的生物利用度，因为它具有广泛的首过代谢。在本研究中，开发并验证了一种以氟康唑为内标物同时测定大鼠血浆中他喷他多和WWJ 01的高度快速和灵敏的UPLC-MS/MS方法。分析物和内标物用甲醇处理，然后在Phenomenex Kinetex® XB‐C18（2.1 × 50 mm × 2.6 μm）色谱柱上分离，流速为0.3 mL/min。移动的流动相为甲醇和水，梯度洗脱。他喷他多、WWJ 01和IS的质量跃迁离子对分别为m/z 222.2 →107.0、m/z 293.2 →71.9和m/z 307.1→220.0。在2-1250 ng/mL（r = 0.995）的浓度范围内观察到良好的线性，他喷他多和WWJ 01的定量下限均为2 ng/mL。所有质控样品的日内和日间准确度和精密度均在± 15%范围内。该方法准确、快速、重现性好，已成功应用于他喷他多和WWJ 01的药代动力学研究。
A prodrug of tapentadol, namely tapentadol carbamate (WWJ01), was synthesized to improve the bioavailability of tapentadol owing to its extensive first‐pass metabolism. In this study, a highly rapid and sensitive UPLC‐MS/MS method was developed and validated for the simultaneous determination of tapentadol and WWJ01 in rat plasma with fluconazole as an internal standard. The analytes and internal standard were treated by methanol and then separated on a Phenomenex Kinetex® XB‐C18 (2.1 × 50 mm × 2.6 μm) column at a flow rate of 0.3 mL/min. The mobile phase comprised methanol and water with a gradient elution. The mass transition ion‐pairs were m/z 222.2 →107.0, m/z 293.2 →71.9 and m/z 307.1→220.0 for tapentadol,.WWJ01 and IS, respectively. Excellent linearity was observed over the concentration range of 2–1250 ng/mL (r = 0.995) with a lower limit of quantification of 2 ng/mL for both tapentadol and WWJ01. The intra‐ and inter‐day accuracy and precision for all quality control samples were within ±15%. The validated method was accurate, rapid and reproducible, and was successfully applied to a pharmacokinetic study of tapentadol and WWJ01.