2-(2-羟基)丙酰氨基-苯甲酸颗粒剂的大鼠体内生物利用度研究

Study on bioavailability of 2-(2-hydroxypropana mido)benzoic acid granules in rat

目的建立一种RP-HPLC方法测定大鼠血浆中2-(2-羟基)丙酰氨基-苯甲酸(HPABA)的浓度,并应用于HPABA颗粒剂在大鼠体内的生物利用度研究。方法色谱柱为Thermo BDS HYPERSIL C_(18)(150 mm×4.6 mm,5μm),流动相为A-乙腈,B-0.1%冰醋酸水溶液,梯度洗脱,检测波长为250 nm,流速为1.0 mL·min^(-1),采用乙酸乙酯液液萃取法处理血浆样品,RP-HPLC方法检测大鼠血浆中HPABA的浓度。结果 HPABA质量浓度在0.05～50 mg·L^(-1)内具有良好的线性关系(r=0.9948),定量下限为0.05 mg·L^(-1),日内和日间精密度均小于13.1%,准确度在(1.1～4.9)%范围内,平均提取回收率为(90.3±12.8～101.4±11.5)%。HPABA颗粒剂在大鼠血浆中的药动学参数为:ρ_(max)、T_(max)、AUC_(0-t)、t_(1/2)和CL值分别为(10.71±1.08) mg·L^(-1),(0.4±0.22) h,(26.18±2.09) mg·L^(-1)·h,(3.51±2.07) h和(1.88±0.13) L·h^(-1)·kg^(-1)。绝对生物利用度为39.5%,表明HPABA颗粒剂在大鼠体内具有较好的口服生物利用度。结论该法适用于HPABA颗粒剂在大鼠体内的生物利用度研究。

Objective To develop an RP-HPLC method for the determination of 2-(2-hydroxypropanamido)benzoic acid(HPABA)in rat plasma and apply the method to study the bioavailability of HPABA granules in rat.Methods After liquid-liquid extraction by ethyl acetate,the separation was achieved on a Thermo BDS HYPERSIL C18(150 mm×4.6 mm,5μm)using a mobile phase consisting of solvent A(acetonitrile)and solvent B(0.1%glacial acetic acid)at a flow rate of 1.0 ml·min-1.The plasma concentration after single oral administration of 50 mg·kg-1HPABA granules to rat was detected by RP-HPLC method.Results The calibration curve was linear over the range of 0.05~50 mg·L-1and the lower limit of quantification(LLOQ)was 0.05 mg·L-1.The intra-and inter-day precision was less than 13.1%and the accuracy(relative error)of HPABA was within(1.1~4.9)%.The average recoveries were(90.3±12.8~101.4±11.5)%.The main pharmacokinetic parameters were as follows:ρmax,Tmax,AUC0-t,t1/2 and CL were(10.71±1.08)mg·L-1,(0.4±0.22)h,(26.18±2.09)mg·L-1·h,(3.51±2.07)h and(1.88±0.13)L·h-1·kg-1,respectively.Conclusion This RP-HPLC method is suitable for the determination of HPABA in rat plasma.