title: A rapid and sensitive LC-MS/MS method for determination of lercanidipine in human plasma and its application in a bioequivalence study in Chinese healthy volunteers.
abstract: A rapid and highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the determination of lercanidipine (LER) in human plasma. The plasma sample was deproteinized with methanol after addition of diazepam (internal standard, IS) and separated on a 38°C Hedera ODS-2 analytical column with a mobile phase of methanol and 5mM ammonium acetate buffer solution containing 0.1% formic acid at an isocratic flow rate of 400μL/min. The detection was performed on an API 4000 tandem mass spectrometer coupled with electrospray ionization (ESI) source in positive ESI mode. Quantification was conducted by multiple reaction monitoring (MRM) of the transitions of m/z 612.2→280.2 for LER and m/z 285.1→193.1 for IS, respectively. The method exhibited high sensitivity (LLOQ of 0.015ng/mL) and good linearity over the concentration range of 0.015-8.0ng/mL. No matrix effect and carry-over effect were observed. The values on both the occasions (intra- and inter-day) were all within 15% at three concentration levels. This robust method was successfully applied in a bioequivalence study to evaluate the pharmacokinetics of LER in 59 healthy male Chinese volunteers after a single oral administration of 10mg LER.
authors.affiliation: Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, 563099, China.
authors.forename: Fuguo
authors.initials: F
authors.lastname: Shi
authors.affiliation: Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang 110004, China. Electronic address: jianlyyxb@163.com.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Jian
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: dinglicpu@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods; D018592:Cross-Over Studies; D004095:Dihydropyridines / Q000097:blood* / Q000737:chemistry*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D010949:Plasma / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods; D013810:Therapeutic Equivalency
chemical_list: D004095:Dihydropyridines; C060343:lercanidipine
keywords: Bioequivalence; Human plasma; LC–MS/MS; Lercanidipine; Sensitive