A high-sensitivity LC-MS/MS method for the determination of 4-methyl-piperazine-1-carbodithioc acid 3-cyano-3, 3-diphenylpropyl ester hydrochloride in rat plasma and its application to a pharmacokinetics study.
4-Methyl-piperazine-1-carbodithioc acid 3-cyano-3, 3-diphenylpropyl ester hydrochloride (TM208), a newly synthesized anticancer compound, was quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the first time. A simple, rapid and sensitive assay method using propranolol as internal standard (IS) after one-step precipitation with acetonitrile was developed and validated to determine TM208 in rat plasma. Separation was achieved on a reverse-phase C(18) column with a mobile phase composed of methanol-water (pH4.0) containing 5 m m ammonium acetate in gradient elution mode. A triple quadrupole tandem mass spectrometer with electrospray ionization source was used as detector and operated by multiple reaction monitoring in the positive ion mode. Calibration curves were linear (r > 0.99) between 0.2 and 500 ng/mL. The quantitative limit was 0.2 ng/mL; reliable precision and accuracy were validated by relative standard deviation values in the range 3.44-13.15% and relative error values between -0.58 and -9.78%. The method was successfully applied to preclinical pharmacokinetic studies of TM208.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Science, Peking University, Beijing, China.
Xiwei
X
Ji
Ye
Y
Chen
Runtao
R
Li
Tianyan
T
Zhou
Wei
W
Lu
D000818:Animals; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D016014:Linear Models; D008297:Male; D010879:Piperazines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
C522133:4-methylpiperazine-1-carbodithioc acid 3-cyano-3,3-diphenylpropyl ester hydrochloride; D010879:Piperazines