Simultaneous determination of simvastatin, simvastatin acid and rivaroxaban in rat plasma by LC-MS/MS
10.13699/j.cnki.1001-6821.2019.07.024
- VernacularTitle:LC-MS/MS测定大鼠血浆中辛伐他汀、辛伐他汀酸和利伐沙班浓度的方法建立
- Author:
Xue-Qin ZHANG
1
;
Xing-Shuo YIN
;
Hao-Yu WANG
;
Wen-Juan HE
;
Qian SUN
;
De-Qiang LI
;
Shu-Mei WANG
Author Information
1. 河北医科大学 第二医院 药学部
- Keywords:
simvastatin;
simvastatin acid;
rivaroxaban;
LC-MS/MS;
blood concentration
- From:
The Chinese Journal of Clinical Pharmacology
2019;35(7):682-685,693
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish a HPLC-MS/MS method for simultaneous determination of the concentration of simvastatin, simvastatin acid and rivaroxaban in rats plasma. Methods The plasma samples were determined after secondary extraction with ethyl acetate. Ticagrelor and lovastatin were used as internal standards. Simvastatin, simvastatin acid and rivaroxaban in rats plasma were separated by Waters C18 (150. 0 mm × 4. 6 mm, 3. 5 μm) with mobile phase consisting of acetonitrile?ammonium (75: 25, pH = 4. 5) . Electrospray ionization source was applied and operated in positive multiple reaction monitoring mode. Polarlity switch (negative-positive mode) was performed. The detector was operated in multiple reaction-monitoring mode at m/z 436. 0→144. 9 for simvastatin, m/z 452. 9 → 162. 3 for simvastatin acid, m/z 324. 1 →127. 2 for rivaroxaban, m/z 521. 1→361. 2 for Ticagrelor and m/z 405. 3→199. 0 for lovastatin. The specificity, standard curve and lower limit ofquantification, precision and recovery, stability and matrix effect of the method were investigated. Results The linear ranges of simvastatin, simvastatin acid and rivastatin in plasma were 1-100, 5-400 and 1-100 ng·m L-1, standard curve were y = 0. 78 x + 7. 00 × 10-4 (r = 0. 992 8) , y = 0. 59 x + 2. 57 × 10-2 (r = 0. 997 2) and y = 1. 09 x + 1. 79 ×10-2 (r = 0. 996 4) , and the lower limit of quantitation were 1, 5 and 1 ng·m L-1, respectively. The intra-day and inter-day standard deviation were less than 15％, and the recovery rate reached more than 70％. The plasma samples had a good stability with freezing-thawing for three times, -80 ℃ for 5 days and 4 ℃ for 24 h. And there was no obvious matrix effect. Conclusion The method was simple, specific and sensitive, suitable to detect a number of samples for pharmacokinetic study.
