title: Simultaneous determination of lovastatin and its metabolite lovastatin acid in rat plasma using UPLC-MS/MS with positive/negative ion-switching electrospray ionization: Application to a pharmacokinetic study of lovastatin nanosuspension.
abstract: Lovastatin (LOV) is an antihyperlipidemic agent which exhibits low bioavailability due to its poor solubility. Therefore, a nanosuspension (NS) was developed as an efficient strategy to improve its oral bioavailability. To evaluate the pharmacokinetics of LOV-NS, a novel, sensitive, and rapid UPLC-MS/MS method was developed and validated for the simultaneous determination of LOV and its metabolite lovastatin acid (LOVA) in rat plasma. Simvastatin (IS) was chosen as the internal standard, and a liquid-liquid extraction method was used to isolate LOV and LOVA from biological matrices. The analytes were analyzed on an Acquity UPLC BEH C18 column, and a gradient program was applied at a flow rate of 0.2mL/min. Then, a tandem quadrupole mass spectrometer coupled with a positive/negative ion-switching electrospray ionization interface was employed to detect the analytes. Quantitation of the analytes was performed in the multiple reaction monitoring mode to monitor the transitions of m/z 427.1→325.0 for LOV and m/z 441.1→325.0 for IS in the positive ion mode and m/z 421.0→101.0 for LOVA in the negative ion mode, respectively. The method was validated over the concentration range 0.25-500ng/mL (r(2)≥0.99) for both LOV and LOVA. The intra-day and inter-day precision (RSD%) of LOV and LOVA were less than 12.87% and the accuracy (RE%) was less than 5.22%. The average extraction recoveries were 90.1% and 91.9% for LOV and LOVA, and the matrix effects were found to be between 85% and 115%. The stability study showed that both analytes were stable during the experiment. Finally, this method has been successfully applied to a pharmacokinetic study in rats following a single oral dose of 10mg/kg LOV-NS.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Mengran
authors.initials: M
authors.lastname: Guo
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Longshan
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Liaoning Institute for Drug Control, No.7, Chongshan Road, Shenyang 110036, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: graham_pharm@aliyun.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: School of Pharmacy, Henan University, Jinming Road, Kaifeng 475004, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Pu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Bingyang
authors.initials: B
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: He
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: pharm305@126.com.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D016014:Linear Models; D008148:Lovastatin / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D008148:Lovastatin
keywords: Lovastatin; Lovastatin acid; Pharmacokinetics; Rat plasma; Simultaneous determination; UPLC–MS/MS