title: Simultaneous determination of lercanidipine, benazepril and benazeprilat in plasma by LC-MS/MS and its application to a toxicokinetics study.
abstract: We aim to develop a rapid, simple, sensitive and specific LC-MS/MS method for the simultaneous quantification of lercanidipine, benazepril and benazeprilat in plasma. It is performed on the Agilent 6410 LC-MS/MS under the multiple-reaction monitoring (MRM) mode with electrospray ionization. Gliclazide was used as the internal standard (IS). Analytes and IS were extracted from plasma by solid-phase extraction. The reconstituted samples were chromatographed on a Diamond C₁₈(150 mm × 4.6 mm, 5 μm) column. The mobile phase was composed of 0.1% acetic acid-acetonitrile (50:50, v/v), with gradient flow rates: 0.6 mL/min (0-4.55 min); 4.55-4.65 min, 1 mL/min; 1 mL/min (4.65-9.5 min); 9.5-9.6 min, 0.6 mL/min; 0.6 mL/min (9.6-10 min). Method validation demonstrated that the method was of satisfactory specificity, sensitivity, precision and accuracy in linear ranges of 1-2000 ng/mL for lercanidipine, 1-2000 ng/mL for benazepril and 1-1600 ng/mL for benazeprilat, respectively. The precision (RSD%) was better than 15, and the lower limit of quantitation was identifiable and reproducible at 1 ng/mL for the three analytes. The plasma samples were stable after being stored for more than 60 days and after two freeze-thaw cycles (-20 to -25 °C). It is demonstrated that this method was successfully applied to samples from a toxicokinetics study of a compound of lercanidipine and benazepril in beagle dogs.
authors.affiliation: College of Pharmacy, Shandong University, 44 West Wenhua Road, Jinan 250012, PR China.
authors.forename: Keguang
authors.initials: K
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Sha
authors.initials: S
authors.lastname: Liu
authors.forename: Dujuan
authors.initials: D
authors.lastname: Zhang
authors.forename: Yanni
authors.initials: Y
authors.lastname: Teng
authors.forename: Chunmin
authors.initials: C
authors.lastname: Wei
authors.forename: Benjie
authors.initials: B
authors.lastname: Wang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.forename: Guiyan
authors.initials: G
authors.lastname: Yuan
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhao
authors.forename: Ruichen
authors.initials: R
authors.lastname: Guo
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001552:Benzazepines / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004095:Dihydropyridines / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D004285:Dogs; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D004095:Dihydropyridines; C052133:benazeprilat; C044946:benazepril; C060343:lercanidipine