Application of a sensitive and specific LC–MS/MS method for determination of chinensinaphthol methyl ether in rat plasma for a bioavailability study

Chinensinaphthol methyl ether (CME) is a potential pharmacologically active ingredient isolated from the dried plants of Justicia procumbens L. (Acanthaceae). A sensitive and specific LC–MS/MS method was developed and validated for the analysis of CME in rat plasma using buspirone as the internal standard (IS). The analyte was extracted with ethyl acetate and chromatographed on a reverse-phase Agilent Zorbax-C18 110 Å column (50 mm × 2.1 mm, 3.5 μm). Elution was achieved with a gradient mobile phase consisting of water and acetonitrile both containing 0.1% formic acid at a flow rate of 0.40 mL/min. The analytes were monitored by tandem–mass spectrometry with positive electrospray ionization. The precursor/product transitions (m/z) in the positive ion mode were 394.5 → 346.0 and 386.1 → 122.0 for CME and IS, respectively. The assay was shown to be linear over the range of 0.50–500 ng/mL, with a lower limit of quantification of 0.50 ng/mL. The method was shown to be reproducible and reliable with the inter- and intra-day accuracy and precision were within ±15%. The assay has been successfully used for pharmacokinetic evaluation of CME after intravenous and oral administration of 1.80 mg/kg CME in rats. The oral absolute bioavailability (F) of CME was estimated to be 3.2 ± 0.2% with an elimination half-life (t1/2) value of 2.4 ± 0.8 h, suggesting its poor absorption and/or strong metabolism in vivo.

► Chinensinaphthol methyl ether (CME) is a potential pharmacologically active ingredient isolated from the dried plants of Justicia procumbens L. (Acanthaceae).
► A sensitive and specific LC–MS/MS method was developed and validated for the analysis of CME in rat plasma using buspirone as the internal standard (IS).
► The assay was shown to be linear over the range of 0.50–500 ng/mL, with a lower limit of quantification of 0.50 ng/mL.
► The assay has been successfully used for pharmacokinetic evaluation of CME after intravenous and oral administration of 1.80 mg/kg CME in rats.
► The oral absolute bioavailability (F) of CME was estimated to be 3.2 ± 0.2% with an elimination half-life (t1/2) value of 2.4 ± 0.8 h, suggesting its poor absorption and/or strong metabolism in vivo.