两种途径给药后卡铂在雌性大鼠体内的血药浓度测定及药动学研究

摘要

目的:建立测定卡铂血药浓度的方法,并研究iv与ip给药后卡铂在雌性大鼠体内的药动学.方法:采用高效液相色谱法.色谱柱为Agilent TC-C18,流动相为甲醇-水(5:95,V/V),流速为1.0 mL/min,检测波长为229 nm,柱温为25℃,内标为5-溴尿嘧啶,进样量为20μL.24只SD大鼠随机分为4组,每组6只,分别iv、ip卡铂20、40 mg/kg.分别于给药前及给药后0.25、0.5、1、1.5、2、4、6、8、10、12 h经眼眶取血0.5 mL,测定卡铂的血药浓度,采用DAS 2.0药动学软件计算药动学参数.结果:血浆中卡铂质量浓度线性范围为0.30~60.00μg/mL(r=0.9991),日内、日间精密度RSD均小于10%(n=5),稳定性试验峰面积的RSD<10%(n=5),方法回收率为98.7%~102.4%(RSD≤6.08%,n=5),提取回收率为83.38%~85.45%(RSD≤5.97%,n=5).雌性大鼠iv卡铂20、40 mg/kg和ip卡铂20、40 mg/kg后的AUC0-12 h分别为(15.503±4.172)、(23.402±4.266)、(6.716±2.306)、(9.384±2.205)μg·h/mL,AUC0-∞分别为(16.424±4.846)、(23.404±4.266)、(6.790±2.378)、(9.765±2.095)μg·h/mL,t1/2z分别为(1.246±0.765)、(0.394±0.058)、(0.513±0.156)、(0.884±0.460)h,tmax分别为(0.700±0.274)、(0.400±0.335)、(0.542±0.368)、(0.833±0.289)h.结论:该方法简便、经济、准确,内标适宜,可用于卡铂在雌性大鼠血浆中的血药浓度测定及药动学研究.%OBJECTIVE:To establish a method for the plasma concentration determination of carboplatin,and study the phar-macokinetics of carboplatin in female rats after intravenous injection and intraperitoneal injection. METHODS:HPLC was per-formed on the column of Agilent TC-C18 with mobile phase of methanol-water(5:95,V/V)at a flow rate of 1.0 mL/min,detection wavelength was 229 nm,and column temperature was 25 ℃. The inner standard was 5-bromouracil,and injection volume was 20 μL. 24 SD rats were randomly divided into 4 groups,6 in each group. The rats were intravenously injected and intraperitoneally in-jected carboplatin 20,40 mg/kg respectively. 0.5 mL blood sample was taken from eyes before administration and after administra-tion of 0.25,0.5,1,1.5,2,4,6,8,10,12 h. The plasma concentration of carboplatin was determined,and DAS 2.0 was used to calculate the pharmacokinetic parameters. RESULTS:The linear range of carboplatin in plasma was 0.30-60.00 μg/mL (r=0.9991);RSDs of intra-day,inter-day precision were lower than 10%(n=5);RSD of peak area in stability test was lower than 10%(n=5);method recovery was 98.7%-102.4%(RSD≤6.08%,n=5),and extraction recovery was 83.38%-85.45%(RSD≤5.97%,n=5). AUC0-12 h of carboplatin 20,40 mg/kg by intravenous injection and intraperitoneal injection in female rats were (15.503 ± 4.172),(23.402 ± 4.266),(6.716 ± 2.306),(9.384 ± 2.205)μg·h/mL;AUC0-∞ were (16.424 ± 4.846),(23.404 ± 4.266),(6.790±2.378),(9.765±2.095)μg·h/mL;t1/2z were(1.246±0.765),(0.394±0.058),(0.513±0.156),(0.884±0.460) h;and tmax were(0.700±0.274),(0.400±0.335),(0.542±0.368),(0.833±0.289)h,respectively. CONCLUSIONS:The meth-od is simple,economic and accurate,with suitable internal standard,and can be used for the plasma concentration determination of carboplatin in female rats and the pharmacokinetic studies.