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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。
OBJECTIVE: To establish a HPLC method for the simultaneous determination of paracetamol and tramadol hydrochloride in human plasma and bioequivalence studies on two preparations of paracetamol tramadol. Methods: The plasma samples were separated by liquid-liquid extraction using diprophylline as internal standard and Kromasil C 6 H 6 column (250 mm × 4.6 mm, 5 μm) with methanol-0.3% formic acid-0.05 mol·L -1 tetrabutylchloride Ammonium sulfate solution (26:62:12) as the mobile phase, simultaneous detection of paracetamol and tramadol by UV-fluorescence detector in series. UV detection wavelength: 245nm; fluorescence excitation wavelength: 275nm, emission wavelength: 304nm. Twenty healthy volunteers took the bioequivalence study of two formulations based on plasma concentrations of acetaminophen and tramadol over time. Results: The minimum limit of quantification of acetaminophen in this method was 0.10μg · mL-1 with a linear range of 0.1000-10.00μg · mL-1. The intra-day RSD was 3.9% -8.0% and the intraday RSD was 5.5% -6.7% The lowest limit of quantitation (MTT) of tramadol was 10.03ng · mL-1 and the linear range was 10.03 ~ 401.0ng · mL-1. The intra-day RSD was 1.9% -5.9% and the intraday RSD was 3.4% -7.3%. The relative bioavailability of acetaminophen in the test preparations was (96.1 ± 15.0)% and the relative bioavailability of tramadol was (93.9 ± 15.3)%. Conclusion: The method is simple, sensitive and can be used for the determination of clinical blood concentration. The test formulation is bioequivalent to the reference formulation.