高效液相色谱法串联紫外-荧光检测器同时测定人血浆中对乙酰氨基酚与盐酸曲马多的浓度  

HPLC determination of paracetamol and tramadol hydrochloride in plasma in series with ultraviolet and fluorescence detection

作　　者：李娟[1] 苏梦翔[2] 丁黎[1,3] 狄斌[1,3] 鲁涓[1] 王晶[1] 陆铭[1] 

机构地区：[1]中国药科大学药物分析教研室,南京210009 [2]中国药科大学药学实验教学中心,南京210009 [3]药物质量与安全预警教育部重点实验室,南京210009

出　　处：《药物分析杂志》2009年第7期1088-1092,共5页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立一种高效液相色谱法,用于人血浆中对乙酰氨基酚和盐酸曲马多浓度的同时测定,并对氨酚曲马多片的2种制剂进行生物等效性研究。方法:血浆样品经液-液萃取,以二羟丙茶碱为内标,采用KromasilC6H6色谱柱(250mm×4.6mm,5μm),以甲醇-0.3%甲酸-0.05mol·L-1四丁基氯化铵溶液(26∶62∶12)为流动相,紫外-荧光检测器串联法同时在线检测对乙酰氨基酚与曲马多,紫外检测波长:245nm;荧光激发波长:275nm,发射波长:304nm。20名健康志愿者服药后,依据血浆中对乙酰氨基酚与曲马多经时血药浓度,对2种制剂进行了生物等效性研究。结果:本法中对乙酰氨基酚最低定量限为0.10μg·mL-1,线性范围为0.1000～10.00μg·mL-1,日内RSD为3.9%～8.0%,日间RSD为5.5%～6.7%;曲马多最低定量限为10.03ng·mL-1,线性范围为10.03～401.0ng·mL-1,日内RSD为1.9%～5.9%,日间RSD为3.4%～7.3%。受试制剂中对乙酰氨基酚的相对生物利用度为(96.1±15.0)%,曲马多的相对生物利用度为(93.9±15.3)%。结论:本方法操作简便、灵敏度高,可用于临床血药浓度测定。受试制剂与参比制剂生物等效。Objectives：To establish an HPLC method for the determination of paracetamol and tramadol hydrochloride in human plasma and to evaluate the bioequivalence of two kinds of paracetamol/tramadol hydrochloride preparations. Methods ：The plasma sample was liquid -liquid extracted,diprophylline was used as an internal standard. The chromatographic separation was performed on a Kromasil C6H6 column（250 mm× 4. 6 mm,5 μm）using methanol -0. 3% formic acid - 0. 05 mol·L^-1 tetrabutyl ammonium chloride （26： 62： 12） as mobile phase,paracetamol and tramadol in human plasma was determined simuhaneously with in series of ultraviolet and fluorescence detection. The ultraviolet detector wavelength was at A = 245 nm,the fluorimetric excitation and emission wavelength were set at 275 nm and 304 nm. The bioequivalence of 2 kinds of preparations was studied according to the concentrations of paracetamol and tramadol in human plasma via time. Results：The lower limit of quantification was 0. 10 μg·mL^-1 for paracetamol,the calibration curve was linear in the range of 0. 1000 μg·mL^-1 to 10.00μg·mL^-1 , the intra -day RSD was 3.9% - 8. 0% ,the inter -day RSD was 5. 5% -6. 7% ;The lower limit of quantification was 10. 03 ng·mL^-1 for tramadol,the calibration curve was linear in the range from 10. 03 ng·mL^-1 to 401.0 ng·mL^-1 ,the intra - day RSD was 1.9% - 5. 9% ,the inter -day RSD was 3. 4% -7. 3%. The relative bioavailability of paracetamol in test preparations was（96. 1 ± 15. 0 ）% ,and that of tramadol in test preparations was（93. 9 ± 15. 3 ）%. Conclusion：The method is accurate and convenient, and suitable for clinical pharmacokinetic study,the test and reference preparations are bioequivalent.

关 键 词：高效液相色谱法 对乙酰氨基酚 盐酸曲马多 生物等效性 

分 类 号：R917[医药卫生—药物分析学]