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-C_(18),流动相为甲醇-水(5∶95,V/V),流速为1.0 m L/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 m L,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/m L(r=0.999 1),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AUC_(0-12h)分别为(15.503±4.172)、(23.402±4.266)、(6.716±2.306)、(9.384±2.205)μg·h/m L,AUC0-∞分别为(16.424±4.846)、(23.404±4.266)、(6.790±2.378)、(9.765±2.095)μg·h/m L,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 pharmacokinetics of carboplatin in female rats after intravenous injection and intraperitoneal injection. METHODS：HPLC was performed on the column of Agilent TC-C_（18） 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 20μL. 24 SD rats were randomly divided into 4 groups,6 in each group. The rats were intravenously injected and intraperitoneally injected carboplatin 20,40 mg/kg respectively. 0.5 mL blood sample was taken from eyes before administration and after administration 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/m L（r=0.999 1）;RSDs of intra-day,inter-day precision were lower than 10%（n=5）;RSD of peak area in stability test was lower than10%（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）. AUC_（0-12） hof 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/m L;AUC0-∞were（16.424 ± 4.846）,（23.404 ±4.266）,（6.790±2.378）,（9.765±2.095）μg·h/m L;t1/2zwere（1.246±0.765）,（0.394±0.058）,（0.513±0.156）,（0.884±0.460）h;and tmaxwere（0.700±0.274）,（0.400±0.335）,（0.542±0.368）,（0.833±0.289）h,respectively. CONCLUSIONS：The method 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.
出处
《中国药房》
CAS
北大核心
2017年第22期3087-3090,共4页
China Pharmacy
基金
唐都医院科技创新发展基金(No.2015LCYJ016)
