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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 )
OBJECTIVE To establish an HPLC ESI MS method for the determination of glyburide in human plasma and investigate the pharmacokinetics of glyburide in combination with metformin in volunteers. Method Determination of glyburide in human plasma samples: The plasma samples were acidified with 1mol·L-1 hydrochloric acid and extracted with ethyl acetate. HPLC ESI MS analysis was performed on a Lichrospher C18 column (dp 5μm, 4 6mmID × 25cm ), The mobile phase was methanol-10mmol·L-1 aqueous solution of ammonium acetate (78:22, V / V). The detection mode was SIM and the detection ion was m / z 492 1 (glibenclamide) 444 1 (internal standard). Twenty healthy volunteers were given oral administration of the test and reference tablets at a dose of 25 mg of glyburide and 50 mg of metformin hydrochloride respectively. Results The linear relationship between the ratio of peak area of glibenclamide to peak area of internal standard and concentration was good in the range of 0 3 10 ~ 413 μg · L -1. The T1 / 2 of glibenclamide test formulation and reference formulation were (54 ± 0 8) h, (59 ± 1 0) h, and Cmax were (14 6 ± 2 2) μg · L- 1 , (12 3 ± 16) μg · L -1, Tmax were (27 ± 0 9) h and (30 ± 0 7) h respectively, and AUC 0 ~ 36 were 73 0 ± 14 0 μg · h · L 1, (63 2 ± 117) μg · h · L -1. The T1 / 2 of metformin and reference preparations were (3 0 ± 0 6) h, (3 0 ± 0 4) h , Cmax were (1 61 ± 0 3 2) mg · L -1, (1 62 ± 0 3 3) mg · L -1, respectively, and T max were (1 8 ± 0 2) h and 1 7 ± 0 4 ) h, AUC0 ~ 15 were (7 3 7 ± 1 3 4)