title: Determination of chamaechromone in rat plasma by liquid chromatography-tandem mass spectrometry: application to pharmacokinetic study.
abstract: A rapid, simple and accurate method was developed for the determination of chamaechromone in rat plasma using liquid chromatography tandem mass spectrometry (LC-MS-MS). Rosuvastatin was used as the internal standard. The plasma samples were extracted by liquid-liquid extraction with ethyl acetate. Chromatographic separation was performed on Xbridge™ C(18) column (2.1mm×50mm, 3.5μm) with linear gradient elution using water and methanol, both of which were acidified with 0.1% aqueous formic acid. The flow rate was 0.4mL/min and the total run time was 6min. Detection was performed on a triple-quadrupole tandem mass spectrometer using positive ion mode electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. The MS/MS ion transitions monitored were m/z 543.3→198.9 and 481.9→258.3 for chamaechromone and rosuvastatin, respectively. Good linearity was observed over the concentration range of 8-6400ng/mL in 0.1mL of rat plasma. The lowest concentration (8ng/mL) in the calibration curve was estimated as LLOQ with both deviation of accuracy and RSD of precision <20% (n=6). Intra-assay and inter-assay variability were less than 11% in plasma. This method was successfully applied to a pharmacokinetic study of chamaechromone in rats after intravenous (5mg/kg) and oral (100mg/kg) administration. Following oral administration the concentration-time curve of chamaechromone exhibited a biphasic absorption profile. The maximum mean concentration in plasma (C(max), 795.9±14.6ng/L) was achieved at 11.3±0.8h (T(max)) and the area under curve (AUC(0-60)) was 6976.7±1026.9ngh/L. After single intravenously administration of chamaechromone, the essential pharmacokinetic parameters C(max), AUC(0-48) were 4300.7±113.6ng/L and 3672.1±225.4ngh/L, respectively. The result showed that the compound was poorly absorbed with an absolute bioavailability being approximately 8.9%.
authors.affiliation: Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lou
authors.forename: Haihong
authors.initials: H
authors.lastname: Hu
authors.forename: Yao
authors.initials: Y
authors.lastname: Liu
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Yu
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Ping
authors.forename: Lushan
authors.initials: L
authors.lastname: Yu
authors.forename: Huidi
authors.initials: H
authors.lastname: Jiang
authors.forename: Su
authors.initials: S
authors.lastname: Zeng
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002853:Chromatography, Liquid / Q000379:methods*; D047309:Flavones / Q000097:blood*; D005464:Fluorobenzenes / Q000097:blood; D007477:Ions; D008297:Male; D000432:Methanol / Q000737:chemistry; D010936:Plant Extracts / Q000097:blood*; D011743:Pyrimidines / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D000068718:Rosuvastatin Calcium; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013449:Sulfonamides / Q000097:blood; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D047309:Flavones; D005464:Fluorobenzenes; D007477:Ions; D010936:Plant Extracts; D011743:Pyrimidines; D013449:Sulfonamides; C561087:chamaechromone; D000068718:Rosuvastatin Calcium; D000432:Methanol