A rapid and sensitive liquid chromatography-tandem mass spectrometric method for the determination of timosaponin B-II in blood plasma and a study of the pharmacokinetics of saponin in the rat.
A rapid, sensitive and selective liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of Timosaponin B-II (TB-II), a pharmacologically active constituent isolated from Anemarrhena asphodeloides. This method was used to examine the pharmacokinetics and bioavailability of TB-II in rats using ginsenoside Re as an internal standard. After simple protein precipitation of the plasma samples with acetonitrile, the analytes were separated on an ODS column (150 mm x 2.1 mm i.d., 5 microm) with the mobile phase of acetonitrile-water (35:65, v/v) containing 0.05% formic acid and detected by electrospray ionization mass spectrometry in the negative multiple reaction monitoring (MRM) mode with a chromatographic run time of 3.0 min. The calibration curves were linear over the range of 5-15,000 ng/ml and the lower limit of quantification (LLOQ) was 5 ng/ml in rat plasma. In this range, relative standard deviations (R.S.D.) were <7.4% for intra-day precision and <9.0% for inter-day precision. The accuracy was within the range of 97.7-107.3%. The method was successfully applied to assess the pharmacokinetics and oral bioavailability of TB-II after intravenous and oral administration in rats, with the oral bioavailability being only 1.1%.
Cai
Fei
F
Department of Pharmacy, Changzheng Hospital, Second Military Medical University, No. 415 Fengyang Road, Shanghai 200003, PR China.
Sun
Lianna
L
Gao
Shouhong
S
Yang
Yang
Y
Yang
Qi
Q
Chen
Wansheng
W
D031403:Anemarrhena / Q000737:chemistry; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002138:Calibration; D004355:Drug Stability; D005615:Freezing; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D015394:Molecular Structure; D008970:Molecular Weight; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D012503:Saponins / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013256:Steroids / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors
D012503:Saponins; D013256:Steroids; C523027:timosaponin B-II