【摘要】 目的　建立人血浆中格列本脲的HPLC ESI MS测定法 ,研究志愿者口服格列本脲与二甲双胍的复方片剂后的药代动力学行为。方法　人血浆样品中格列本脲的测定方法 :血浆样品以 1mol·L- 1的盐酸酸化后用乙酸乙酯提取 ,进行HPLC ESI MS分析 ,色谱柱为LichrospherC18(dp 5μm ,4 6mmID× 2 5cm ) ,流动相为甲醇 -10mmol·L- 1醋酸铵水溶液 (78∶2 2 ,V/V) ,检测方式为SIM方式 ,检测离子为m/z 492 1(格列本脲 )、m /z 444 1(内标 )。 2 0名健康志愿者交叉口服供试片和参比片 ,剂量均为格列本脲 2 5mg和盐酸二甲双胍 50 0mg。 结果　在 0 3 10～ 413 μg·L- 1范围内格列本脲峰面积与内标峰面积的比值与浓度的线性关系良好。格列本脲受试制剂与参比制剂的T1/2 分别为(5 4± 0 8)h、(5 9± 1 0 )h ,Cmax 分别为 (14 6± 2 2 ) μg·L- 1、(12 3± 16) μg·L- 1,Tmax分别为 (2 7± 0 9)h、(3 0±0 7)h ,AUC0～ 3 6 分别为 (73 0± 14 0 ) μg·h·L- 1、(63 2± 117)μg·h·L- 1;二甲双胍受试制剂与参比制剂的T1/2 分别为(3 0± 0 6)h、(3 0± 0 4)h ,Cmax分别为 (1 61± 0 3 2 )mg·L- 1、(1 62± 0 3 3 )mg·L- 1,Tmax分别为 (1 8± 0 2 )h、(1 7± 0 4)h ,AUC0～ 15 分别为 (7 3 7± 1 3 4 )更多还原

【Abstract】 AIMTo develop an HPLC-ESI-MS assay for the determination of glyburide in human plasma, and to investigate the pharmacokinetics of glyburide and metformin from their fixed combination tablets in human. METHODSAfter being made acidic with hydrochloric acid, plasma was extracted by ethyl acetate and separated by HPLC on a reversed-phase C18 column ( dp 5 μm , 4.6 mm ID×25 cm ) with a mobile phase of 10 mmol·L -1 ammonium acetate water solution-methanol (22∶78, V/V). HPLC-ESI-MS was performed in the selected ion monitoring (SIM) mode using target ions at m/z 492 1 for glyburide and m/z 444 1 for the internal standard. A randomized crossover design was employed in 20 healthy volunteers. In the two study periods, a single dose of 2 5 mg glyburide and 500 mg metformin hydrochloride were administered to each volunteer. RESULTSCalibration curve for glyburide was linear over the range of 0 310～413 μg·L -1 The pharmacokinetic parameters T 1/2 , C max , T max and AUC 0～τ were (5 4±0 8) h, (146±22) μg·L -1 , (2 7±0 9) h and (730±140) μg·h·L -1 for glyburide from the combintion tablet; (5 9±1 0) h, (123±16) μg·L -1 , (3 0±0 7) h and (632±117) μg·h·L -1 for glyburide from the reference glyburide tablet coadministered with metformin; (3 0±0 6) h, (1 61±0 32) mg·L -1 , (1 8±0 2) h and (7 37±1 34) mg·h·L -1 for metformin from the combination tablet; (3 0±0 4) h, (1 62±0 33) mg·L -1 , (1 7±0 4) h and (7 43±1 36) mg·h·L -1 for metformin from the reference metformin tablet coadministered with glyburide, respectively. CONCLUSIONSThe assay proved to be sensitive, accurate and convenient. For glyburide, the mean C max and AUC 0～36 from the combination tablet were both higher than that from the reference glyburide tablet coadministered with metformin. However, for the mean C max and AUC 0～15 for metformin, there was no statistically significant difference between the combination tablet and the reference metformin tablet coadministered with glyburide.更多还原