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

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2012-08, Vol.903, p.75-80
• Main Authors: Zhou, Shujun, Qiu, Feng, Tong, Zhanqi, Yang, Shihai, Yang, Meihua
• Format: Article
• Language: English
• Subjects: Acanthaceae - chemistry; Animals; Assaying; Bioavailability; Buspirone; Chinensinaphthol methyl ether; Chromatography; Chromatography, Liquid - methods; Coronal mass ejection; Drug Stability; Elution; Ethers; Ionization; Justicia procumbens; LC–MS/MS; Least-Squares Analysis; Male; Naphthols - blood; Naphthols - chemistry; Naphthols - pharmacokinetics; Plant Extracts - administration & dosage; Plant Extracts - blood; Plant Extracts - chemistry; Rat; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sensitivity and Specificity; Surgical implants; Tandem Mass Spectrometry - methods
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2012.06.045

► 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 0.50–500ng/mL, with a lower limit of quantification of 0.50ng/mL. ► 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 (t1/2) value of 2.4±0.8h, 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 analyte was extracted with ethyl acetate and chromatographed on a reverse-phase Agilent Zorbax-C18 110Å 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 (t1/2) value of 2.4±0.8h, suggesting its poor absorption and/or strong metabolism in vivo.