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  • Title: Simultaneous determination of tapentadol and its carbamate prodrug in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study.
    Author: Liu C, Li Y, Yang R, Zhang S, Zhao L, Zhang T.
    Journal: Biomed Chromatogr; 2018 Oct; 32(10):e4300. PubMed ID: 29799633.
    Abstract:
    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.
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