期刊文献+

液相色谱-串联质谱法测定辛伐他汀片的人体药动学和生物等效性 被引量:10

Determination of pharmacokinetics and bioequivalence of simvastatin tablets with LC-MS/MS in Chinese healthy volunteers
下载PDF
导出
摘要 目的:建立人血浆中辛伐他汀浓度的液相色谱-串联质谱(LC-MS/MS)测定法,研究健康受试者单剂量口服辛伐他汀受试或参比制剂后的药动学和生物等效性。方法:20名健康男性受试者进行随机双交叉试验,分别单剂量口服20 mg辛伐他汀受试制剂和参比制剂,采用LC-MS/MS以洛伐他汀为内标正离子选择性反应检测测定辛伐他汀血浆浓度,计算两者的药动学参数及相对生物利用度。结果:受试制剂和参比制剂的血药浓度水平一致,主要药动学参数如下:c_(max)分别为(8.0±s 1.9)和(8.1±1.8)μg·L^(-1);t_(max)分别为(1.9±0.3)和(1.9±0.3)h;t_(1/2)分别为(3.7±1.4)和(4.1±2.2)h;AUC_(0~24)分别为(30±8)和(30±6)μg·h·L^(-1);AUC`(0~∞)分别为(30±8)和(31±7)μg·h·L^(-1)。由2种制剂的AUC_(0~24)计算,受试制剂的相对生物利用度为(101±20)%。结论:建立的LC-MS/MS测定法专属、准确、灵敏度适宜。测得辛伐他汀受试制剂和参比制剂生物等效。 AIM:To establish a LC-MS/MS method for the study of the pharmacokinetics and bioequivalence of simvastatin tablets or reference tablets in healthy male Chinese volunteers. METHODS : A single oral dose of 20 mg simvastatin tablets or reference tablets was given to each volunteer according to an open randomized crossover study in 20 healthy males. The concentrations of simvastatin and reference preparations in plasma were determined by LC-MS/MS with positive ion SRM detection using lovastatin as internal standard. The pharmacokinetics and bioavailability were calculated and compared. RESULTS:The main pharmcokinetic parameters after po a single dose of 20 mg simvastatin and reference tablets individually were as follows: cmax (8.0±s 1.9) and (8.1 ± 1.8) μg·L^-1, tmax (1.9±0.3) and (1.9±0.3) h, t1/2 (3.7± 1.4) and (4.1±2.2) h, AUC0-24 (30 ± 8) and (30 ± 6) μg·L^-1, AUC0-∞ (30 ± 8) and (31 ± 7) μg·L^-1, respectively. The relative bioavailability of the test compared to reference tablets was (101± 20) %. CONCLUSION: The LCMS/MS method is proved to be specific and sensitive. The simvastatin tablets are bioequivalent to the equivalent dose of reference preparation.
出处 《中国新药与临床杂志》 CAS CSCD 北大核心 2007年第5期347-351,共5页 Chinese Journal of New Drugs and Clinical Remedies
关键词 辛伐他汀 药动学 色谱法 高压液相 光谱法 质量 电喷雾电离 simvastatin pharmacokinetics chromatography, high pressure liquid spectrometry, mass,electrospray ionization
  • 引文网络
  • 相关文献

参考文献8

二级参考文献21

  • 1俞进.降胆固醇新药──胆固醇合成抑制剂[J].首都医学院学报,1995,16(1):80-81. 被引量:7
  • 2杜志民,曾群英,董吁钢,胡承恒.脂必妥(60例)与辛伐他汀(30例)治疗高脂血症的比较[J].新药与临床,1997,16(1):63-64. 被引量:20
  • 3陈新谦 金有豫.新编药物学,第14版[M].北京:人民卫生出版社,1997.317-318.
  • 4陆宗良 寇文容 等.Simvastatin治疗高脂血症的临床观察[J].中华心血管病杂志,1993,21(4):216-216.
  • 5-.VIDAL 临床用药年鉴[M].北京:中信出版社,1998.517-519.
  • 6Endo A, Kuroda M,Tsuhita Y. ML-236A, ML-236B, and ML236C, new inhibitors of cholesterogenesis produced by peniciuium citrinum, J Antibiot, 1976;29:1346~1348.
  • 7Hisao O, Naotaka U, Kazuhode I, et al. Determination of simvastatin and its active metabolite in human plasma by columnswitching high-performance liquid chromatography with fluorescence detection after derivatization with lbromoacetylpyrene. J Chromatogr B, 1997(694):211~217.
  • 8Endo A, Hasumi K, Tsuhita Y, Momacolins J, et al., new inhibitors of cholesterol biosynthesis produced by monascus rubber, J Antibiot,1985 ;38:420~422.
  • 9Kakano T, Abe S, Hata S.A selected ion monitoring method for quantifying simvastatin and its acid form inhuman plasma using the ferroceneboronate derivative. Biomed. Environ. Mass Spectrom,1990;19:577~581.
  • 10Morris MJ, Gilbert JD, Hiseh JYK. et, al. Determination of the HMG-CoA reductase inhibitors simastatin, lovastatin, and pravastatin in plasma by gas chromatography/chemical ionization mass spectrometry. Mass Spectr, 1993 ;22:1~8.

共引文献62

同被引文献69

引证文献10

二级引证文献25

;
使用帮助 返回顶部