Pharmacokinetics of the pyrimidine nucleoside compound GY005 in SD rats based on liquid chromatography coupled with mass spectrometry experiment
To establish a method LC-MS/MS for the determination of the pyrimidine nucleoside compound GY005 concentration in rat plasma and to study its pharmacokinetics in rats.Terfenadine was used as the internal standard.After the protein was precipitated by acetonitrile-methanol,the plasma samples were separated on the ACE 5 C4(50 mm×2.1 mm,2.5μ m)chromatographic column through gradient elution by water(0.1%formic acid)-acetonitrile(0.1%formic acid)as the mobile phase.The flow rate was 0.7 mL·min-1 and sample volume was 10 μL.Then the analytes were detected by electrospray ionization(ESI)source in with positive ion scanning.The detection conditions of GY005 and internal standard(terfenadine)by mass spectrometry were m/z 445.15 → 270.10 and m/z 472.40 → 436.40,respectively.After the rats were given 2 mg·kg-1 GY005 and the plasma concentration of GY005 was detected at different time points.The pharmacokinetic parameters were calculated.After single intravenous injection GY005(2 mg·kg-1)to male and female rats,the main pharmacokinetic parameters were as follows:male rats:AUClast was(228±44)h·ng·mL-1,T1/2 was(0.30±0.01)h,CL was(149±29)mL·min·kg-1;female rats:AUClast was(215±158)h·ng·mL-1,T1/2 was(0.30±0.03)h,CL was(226±162)mL·min-1·kg-1.There is no significant difference in exposure levels between males and females.This method is simple,sensitive and rapid for pharmacokinetic study of GY005.
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