title: Simultaneous determination of l-tetrahydropalmatine and its active metabolites in rat plasma by a sensitive ultra-high-performance liquid chromatography with tandem mass spectrometry method and its application in a pharmacokinetic study.
abstract: A sensitive and reliable ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for simultaneous determination of l-tetrahydropalmatine (l-THP) and its active metabolites l-isocorypalmine (l-ICP) and L-corydalmine (l-CD) in rat plasma. The analytes were extracted by liquid-liquid extraction and separated on a Bonshell ASB C18column (2.1 × 100 mm; 2.7 μm; Agela) using acetonitrile-formic acid aqueous as mobile phase at a flow rate of 0.2 mL/min in gradient mode. The method was validated over the concentration range of 4.00-2500 ng/mL for l-THP, 0.400-250 ng/mL for l-ICP and 1.00-625 ng/mL for l-CD. Intra- and inter-day accuracy and precision were within the acceptable limits of <15% at all concentrations. Correlation coefficients (r) for the calibration curves were >0.99 for all analytes. The quantitative method was successfully applied for simultaneous determination of l-THP and its active metabolites in a pharmacokinetic study after oral administration with l-THP at a dose of 15 mg/kg to rats.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Weihui
authors.initials: W
authors.lastname: Wang
authors.affiliation: McLean Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Peng
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Wang
authors.affiliation: McLean Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: David Y W
authors.initials: DYW
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Dai
mesh_terms: D000818:Animals; D001600:Berberine Alkaloids / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D057230:Limit of Detection; D051381:Rats; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D001600:Berberine Alkaloids; C014215:tetrahydropalmatine
keywords: UHPLC-MS/MS; l-THP; metabolites; pharmacokinetics