title: Validated UPLC-MS/MS method for simultaneous determination of simvastatin, simvastatin hydroxy acid and berberine in rat plasma: Application to the drug-drug pharmacokinetic interaction study of simvastatin combined with berberine after oral administration in rats.
abstract: A rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay method was developed and validated for simultaneous quantification of simvastatin (SV), its metabolite simvastatin hydroxy acid (SVA) and berberine (BBR) in rat plasma. Separation was performed on Poroshell 120 EC-C18 column (4.6×50mm, 2.7μm) using gradient elution by mobile phase containing acetonitrile and 10mM ammonium acetate (pH 4.5). Polarity switch (positive-negative-positive ionization mode) was performed in a total run time of 4.0min. The lower limits of quantification (LLOQ) for SV, SVA and BBR were 0.10, 0.20 and 0.10ng/mL, respectively. The response function was established for concentration range of 0.10-100ng/mL for SV and BBR and 0.20-3000ng/mL for SVA, with a coefficient of correlation of >0.99 for all the compounds. The proposed method was applied to the drug-drug pharmacokinetic interaction study of SV combined with BBR after oral administration in rats.
authors.affiliation: Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.affiliation: Northeast Pharmaceutical (Shenyang) Science & Technology Development Co., Ltd., Shenyang, China.
authors.forename: Xianying
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Guofei
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Guilian
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, China. Electronic address: lmzhao19@163.com.
authors.forename: Limei
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001599:Berberine / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005260:Female; D057230:Limit of Detection; D016014:Linear Models; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D019821:Simvastatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C532833:simvastatin hydroxyacid; D001599:Berberine; D019821:Simvastatin
keywords: Berberine; Determination; Drug–drug interaction; LC–MS–MS; Pharmacokinetics; Simvastatin