title: Validation of an HPLC-MS-MS assay for determination of morellic acid in rat plasma: application to pharmacokinetic studies.
abstract: A selective and rapid high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) was developed for the quantification of morellic acid in rat plasma. HPLC was performed using a Capcell MG C18 (50 × 4.6 mm, i.d., 5 µm) column, and isocratic elution with water-acetonitrile (20:80, v/v) at a flow rate of 0.5 mL/min. Sample preparation of analyte and internal standard (gambogic acid) involved liquid-liquid extraction using ethyl acetate-isopropanol (1:1, v/v) from 50 µL plasma. The precursor → production transitions for analyte and IS were m/z 559.4 → 471.3, and m/z 627.3 → 583.3, respectively, and were monitored on a triple-quadrupole mass spectrometer, operating in negative ion scan mode. The method was validated across the dynamic concentration range of 20-7,500 ng/mL for morellic acid, with a fast run time of 6.0 min. The analytical method measured concentrations of morellic acid with accuracy (% bias) of ≤6.4% and precision (% RSD) of ≤14.0%. Morellic acid was stable during the battery of stability studies. Finally, the applicability of this assay has been successfully demonstrated in vivo pharmacokinetic studies in Sprague-Dawley rats. This method will therefore be useful for further preclinical and clinical pharmacokinetic studies of morellic acid.
authors.affiliation: Department of Breast Surgery, Liaoning Cancer Hospital and Institute, Shenyang 110042, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, Liaoning Cancer Hospital and Institute, Shenyang 110042, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Breast Surgery, Liaoning Cancer Hospital and Institute, Shenyang 110042, P.R. China daqingjiang@outlook.com.
authors.forename: Daqing
authors.initials: D
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D057230:Limit of Detection; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D044004:Xanthones / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: D044004:Xanthones; C558352:morellic acid