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

摘要

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? column (50mm×2.1mm, 3.5μm). Elution was achieved with a gradient mobile phase consisting of water and acetonitrile both containing 0.1% formic acid at a flow rate of 0.40mL/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 0.50-500ng/mL, with a lower limit of quantification of 0.50ng/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 1.80mg/kg CME in rats. The oral absolute bioavailability (F) of CME was estimated to be 3.2±0.2% with an elimination half-life (t _(1/2)) value of 2.4±0.8h, suggesting its poor absorption and/or strong metabolism in vivo.