Study on the Pharmacokinetics and Absolute Bioavailability of Anti-inflammatory Compound HB0314 in Rats in vivo / 中国药房

ABSTRACT

OBJECTIVE:To establish the detection method for anti-inflammatory compound HB0314 in plasma of rats,and study on its pharmacokinetic characteristics in rats in vivo. METHODS:UPLC-MS/MS was performed on the column of Waters Ac-quity UPLCTM BEH C18 with mobile phase of 0.1% formic acid aqueous solution(A)-methanol(B)by gradient elution(0-2 min, 70%-90% B) at flow rate of 0.25 mL/min,column temperature was 30 ℃,and injection volume was 5 μL. Electrospray ion source was used,capillary voltage was 3 kV,ion source temperature was 150 ℃,desolvation gas temperature was 450 ℃,desol-vent air flow volume was 600 L/h,cone air flow volume was 45 L/h,and the inner standard was tetrahydropalmatine. 12 rats were randomly divided into iv group and ig group,6 in each group. Rats were intravenously injected and intragastrically administrated HB0314 solution 5,10 mg/kg. Sample blood 0.4 mL were taken from the jugular vein blood before administration and after 5,15, 30,60,120,240,360,480,600,720,1440 min of administration to determine the HB0314 plasma concentration. DAS 2.0 software was used to calculate the pharmacokinetic parameters and absolute bioavailability. RESULTS:The linear range of HB0314 was 1-1000 ng/mL(r=0.9955),and the lower limit of quantification was 1 ng/mL. RSDs of extra-day and daytime precision,sta-bility were not higher than 8.45%(n=5);recovery were 68.21%-90.29%(RSD≤11.20%,n=5),and matrix effects were 82.63%-106.90%(RSD≤6.75%,n=5). After intravenous injection and intragastric administration,AUC0-24 h were (270.267 ± 21.164), (252.755 ± 26.169)μg·h/L (n=6);t1/2z were (8.722 ± 2.266),(11.877 ± 4.517) h (n=6);and absolute bioavailability was 56.79%. CONCLUSIONS:The method is rapid,simple,and can be used for the determination of HB0314 content in plasma of rats. HB0314 shows high oral absolute bioavailability in rats in vivo,indicating that post-dosage form design may be considered as oral anti-inflammatory drugs.