固相萃取-HPLC法测定大鼠体内咖啡因、氨苯砜和氯唑沙宗的血药浓度及药动学研究  

Determination of Plasma Concentration of Caffeine,Dapsone and Chlorzoxazone by Solid Phase Extraction-HPLC and Pharmacokinetic Study

作　　者：王海波[1] 杨欣欣[1] 邸学[1] 

机构地区：[1]辽宁中医药大学药学院,辽宁大连116600

出　　处：《中国药房》2015年第34期4770-4772,共3页China Pharmacy

基　　金：国家自然科学基金资助项目(No.81102789)

摘　　要：目的:测定大鼠体内咖啡因、氨苯砜和氯唑沙宗的血药浓度,计算药动学参数。方法:取大鼠6只,ig咖啡因、氨苯砜和氯唑沙宗混合溶液,给药剂量分别为1.5、2、3 mg/kg,于给药前及给药后0.5、1、2、3、4、6、8、12、24 h取血0.2~0.3 ml;血浆样品用固相萃取法处理,采用高效液相色谱法,以N-(2-羟乙基)邻苯二甲酰亚胺为内标,测定咖啡因、氨苯砜和氯唑沙宗的血药浓度;并用DAS 2.0软件计算药动学参数。结果:咖啡因、氨苯砜及氯唑沙宗检测质量浓度的线性范围均为0.2~30μg/ml(r分别为0.996 4、0.996 1、0.998 8),定量限均为0.2μg/ml,低、中、高质量浓度水平的方法回收率分别为(84.8±3.6)%^(111.4±10.2)%(RSD为4.3%~9.8%)、(107.0±13.3)%^(113.5±8.1)%(RSD为7.1%~14.0%)、(104.2±10.8)%^(111.1±12.2)%(RSD为8.0%~11.0%)(n=3);药动学参数tmax为(1.70±0.99)、(1.50±1.00)、(1.92±0.80)h,t1/2为(0.73±0.22)、(2.77±1.35)、(2.78±2.34)h,cmax为(2.60±0.50)、(5.78±1.19)、(9.76±1.37)mg/L,AUC0-t为(8.43±0.79)、(20.68±1.91)、(26.71±2.45)mg·h/L(n=6)。结论:本法操作简便、灵敏度高、结果准确,可用于咖啡因、氨苯砜和氯唑沙宗的血药浓度测定和药动学研究。OBJECTIVE：To determine plasma concentration of caffeine,dapsone and chlorzoxazone in rats,and to calculate pharmacokinetic parameters. METHODS：6 rats were given the mixture of caffeine,dapsone and chlorzoxazone intragastrically,1.5,2 and 3 mg/kg,respectively. 0.2-0.3 ml blood were collected before medication and 0.5,1,2,3,4,6,8,12,24 h after medication.The plasma sample was treated with solid phase extraction. The plasma concentration of caffeine,dapsone and chlorzoxazone were determined by HPLC using N-（2-Hydroxyethyl）phthalimide as internal standard. The pharmacokinetic parameters were calculated using DAS 2.0 software. RESULTS：The linear ranges of caffeine,dapsone and chlorzoxazone were all 0.2-30 μ g/ml（r were 0.996 4,0.996 1,0.998 8,respectively）. The limit of quantitation were 0.2 μg/ml. The recoveries of low-concentration,medium-concentration and high concentration were（84.8±3.6）%-（111.4±10.2）%（RSD were 4.3%-9.8%,n=3）,（107.0±13.3）%-（113.5±8.1）%（RSD were 7.1%-14.0%,n=3）,（104.2±10.8）%-（111.1±12.2）%（RSD were 8.0%-11.0%,n=3）. Pharmacokinetic parameters were as follows as tmax（1.70±0.99）,（1.50±1.00）,（1.92±0.80）h;t1/2（0.73±0.22）,（2.77±1.35）,（2.78±2.34）h;cmax（2.60±0.50）,（5.78±1.19）,（9.76±1.37）mg/L;AUC0-t（8.43±0.79）,（20.68±1.91）,（26.71±2.45）mg·h /L（n=6）.CONCLUSIONS：The method is simple,sensitive and accurate,and can be used for the plasma concentration determination and pharmacokinetic study of caffeine,dapson and chlorzoxazone.

关 键 词：固相萃取 高效液相色谱法 咖啡因 氨苯砜 氯唑沙宗 药动学参数 大鼠 

分 类 号：R965[医药卫生—药理学]