Establishment of a liquid chromatographic/mass spectrometry method for quantification of tetrandrine in rat plasma and its application to pharmacokinetic study.
A rapid and sensitive liquid chromatography-tandem mass spectrometric method (LC/MS/MS) for the determination of tetrandrine in rat plasma has been developed, fully validated and successfully applied to pharmacokinetic study in Sprague-Dawley (SD) rats after a single oral administration. Sample preparation involves a liquid-liquid extraction with n-hexane-dichlormethane (65:35, containing 1% 2-propanol isopropyl alcohol, v/v). Tetrandrine and brodimoprim (internal standard) were well separated by LC with a Dikma C(18) column using acetonitrile-methanol-ammonium formate aqueous solution (20mM) containing 0.3% formic acid (20:30:50, v/v/v) as mobile phase. Detection was performed on a triple quadrupole mass spectrometer in multiple reaction monitoring mode. The ionization was optimized using ESI(+) and selectivity was achieved using MS/MS analysis, m/z 623.0-->381.0 and m/z 339.0-->281.0 for tetrandrine and I.S., respectively. The present method exhibited good linearity over the concentration range of 5-2,000 ng/mL for tetrandrine in rat plasma with a lower limit of quantification of 5 ng/mL. The intra- and inter-day precision were 2.0-9.2% and 4.5-9.4%, and the intra- and inter-day accuracy ranged from -7.6 to 10.3% and -6.0 to 5.3%, respectively. No endogenous compounds were found to interfere with the analysis, and tetrandrine was stable during the whole assay period. The method was successfully applied to a pharmacokinetic study after an intragastric administration (i.g.) of tetrandrine to SD rats with a single dose of 50mg/kg. The results confirm that the assay is suitable for the pharmacokinetic study of tetrandrine.
Song
Naining
N
School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
Zhang
Shaoyu
S
Li
Quansheng
Q
Liu
Changxiao
C
D000818:Animals; D019540:Area Under Curve; D044182:Benzylisoquinolines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D005215:Fasting; D005260:Female; D006207:Half-Life; D007166:Immunosuppressive Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013997:Time Factors; D014295:Trimethoprim / Q000031:analogs & derivatives / Q000737:chemistry
D044182:Benzylisoquinolines; D007166:Immunosuppressive Agents; C009438:tetrandrine; D014295:Trimethoprim; C037079:brodimoprim