title: Quantification of leonurine, a novel potential cardiovascular agent, in rat plasma by liquid chromatography-tandem mass spectrometry and its application to pharmacokinetic study in rats.
abstract: Leonurine (SCM-198), an alkaloid from Herba Leonuri, has been suggested as a novel cardiovascular agent by pharmacology studies in preclinical stage. In present study, we report a simple, rapid and sensitive high-performance liquid chromatography-tandem mass spectrometry method (HPLC-MS/MS) for determination of leonurine in rat plasma. Leonurine and its internal standard (IS) n-benzoyl-l-arginine ethyl ester (BAEE) were extracted from plasma samples by one-step protein precipitation with perchloric acid. Chromatographic separation was performed on an Agilent Zorbax SB-C₁₈ column (150 × 2.1 mm, 5 µm) using an isocratic elution with acetonitrile-ammonium acetate buffer (10 mm, pH 4.0; 25:75, v/v) as mobile phase at a flow rate of 0.2 mL/min. Analytes were detected by tandem mass spectrometry in positive electrospray ionization (ESI) mode using multiple reaction monitoring (MRM) with the transitions of m/z 312.3 → 181.1 for leonurine and m/z 307.2 → 104.6 for IS. The calibration curves were linear over the range of 4-256 ng/mL with a lower limit of quantitation (LLOQ) of 4 ng/mL. The intra- and inter-day assay precision (as relative standard deviation) were <15%, except which at LLOQ were <20%, with accuracy in the range 98.73-105.42%. The validated HPLC-MS/MS method was successfully applied to the pharmacokinetic study in rats following oral administration of leonurine.
authors: School of Pharmacy, Fudan University, Zhangheng Road 826, Pudong District, Shanghai 200032, China.
authors: Qing
authors: Q
authors: Zhu
authors: Weimin
authors: W
authors: Cai
authors: Xianyi
authors: X
authors: Sha
authors: Guo
authors: G
authors: Ma
authors: Yuanting
authors: Y
authors: Zheng
authors: Xueru
authors: X
authors: Shi
authors: Yizhun
authors: Y
authors: Zhu
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D002138:Calibration; D002317:Cardiovascular Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000097:blood; D031332:Leonurus / Q000737:chemistry; D057230:Limit of Detection; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D002317:Cardiovascular Agents; C013587:leonurine; D005707:Gallic Acid; D001120:Arginine; C009727:benzoylarginine ethyl ester