抗炎化合物HB0314在大鼠体内的药动学及绝对生物利用度研究  

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

作　　者：唐俏欣 许俊鹏[1,2] 潘超[1,2] 汤明海[2] 万丽[1] 

机构地区：[1]成都中医药大学药学院,成都611137 [2]四川大学华西医院生物治疗国家重点实验室,成都610041

出　　处：《中国药房》2017年第28期3915-3918,共4页China Pharmacy

基　　金：国家自然科学基金资助项目(No.81374017)

摘　　要：目的:建立大鼠血浆样品中抗炎化合物HB0314的检测方法,并研究其在大鼠体内的药动学特征。方法:采用超高效液相色谱-串联质谱法(UPLC-MS/MS),色谱柱为Waters Acquity UPLC^(TM)BEH C_(18)柱,流动相为0.1%甲酸水溶液(A)-甲醇(B),梯度洗脱(0~2 min,70%~90%B),流速为0.25 mL/min,柱温为30℃,进样量为5μL;采用电喷雾离子源,毛细管电压为3 k V,离子源温度为150℃,脱溶剂气温度为450℃,脱溶剂气流量为600 L/h,锥孔气流量为45 L/h,内标为延胡索乙素。将12只大鼠随机分成iv组和ig组,每组6只,分别iv、ig HB0314溶液5、10 mg/kg,分别于给药前及给药后5、15、30、60、120、240、360、480、600、720、1 440 min取颈静脉血0.4 mL测定HB0314血药浓度,采用DAS 2.0软件计算药动学参数并计算绝对生物利用度。结果:HB0314质量浓度在1~1 000 ng/mL内线性关系良好(r=0.995 5),定量下限为1 ng/mL;日内、日间精密度、稳定性的RSD≤8.45%(n=5);回收率为68.21%~90.29%(RSD≤11.20%,n=5);基质效应为82.63%~106.90%(RSD≤6.75%,n=5)。iv与ig给药后,HB0314在大鼠体内的AUC_(0-24 h)分别为(270.267±21.164)、(252.755±26.169)μg·h/L(n=6),t1/2z分别为(8.722±2.266)、(11.877±4.517)h(n=6),绝对生物利用度为56.97%。结论:本方法快速、简便,可用于大鼠血浆中HB0314含量的测定。HB0314在大鼠体内具有较高的绝对生物利用度,提示后期剂型设计可考虑将其制成口服剂。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.

关 键 词：HB0314 超高效液相色谱-串联质谱法 大鼠 药动学 绝对生物利用度 

分 类 号：R969.1[医药卫生—药理学]