2016 Jun % μl 5 min ESI mg / 120 μl 1. 5 ml 15 μl A min 500 μl B = 8 2

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1 646 CN /R ISSN http / /www. cjcpt. com 2016 Jun pravastatin sodium 1S- 1α βs * δs * 2α SD 15 mg /kg6α8β R * 8aα a- -β δ DAS FDA 3 F A T max C max AUC t 1 / A HMG-CoA LC-MS R969 A ZX ZX NA3 zhaoyingsky@ imm. ac. cn Tel dugh@ imm. ac. cn

2 2016 Jun % μl 5 min ESI mg / 120 μl 1. 5 ml 15 μl A min 500 μl B = min r /min 10 min 490 μl C μl D % 0. 05% E = min 1. 2 SPF SD 200 ~ ESI Agilent AllegraTM X-22R Beckman min h Vortex-Genie ml 4 Organomation N-EVAP r /min 10 min - 40 Organomation 1. 6 Eppendorf Eppendorf 1. 4 Agilent ZORBAX SB-C mm 50 mm 3. 5 μm USA % 0. 05% = V /V 0. 3 ml /min V L /min 35 psig V V mg 1 ml 1 mg /ml = mg 1 ml 1 mg /ml 1 μg /ml r /min 5 min 50 μl 240 g 10 μl SYXK Agilent G1379B G1311A SD G1329A G1315DDAD 6 12 h G1316A mg /kg - DAS

3 648 Chin J Clin Pharmacol Ther 2016 Jun min 3. 0 min 2. 1 LC-MS 2 2 LC-MS A B C + + D μg /L μg /L μg /L μg /L 50 μg /L 400 μg /L 5 A i 5 3 d A s Y X μg /L 2 RSD Y = X r = ~ 6% 2 x ± s n = 5 μg /L μg /L n = 5 RSD % μg /L n = 3 RSD % ± ± ± ± ± ± μg /L 5 50 μg /L 400 μg /L 70% 15 μl

4 2016 Jun μg /L 50 μg /L 400 μg /L 5 15 μl % 3 3 x ± s n = 5 μg /L % RSD % % RSD % ± ± ± ± ± ± AUC t 1 /2 3 SPSS t 3 F 1 2 A T max F A P < T max C max 3 x ± s n = 6 A AUC 0 - t B t 1 /2 C T max D C max 1 2 A 3 F 1 2 A c P < F % A 7

5 650 Chin J Clin Pharmacol Ther 2016 Jun B x ± s n = ± ng ml - 1 h ± ng ml - 1 h DAS t 1 /2 3 A 3 - area under the curve AUC D 1 C max ± μg /L3 C max ± μg /L T max C 4 t max h 5 T max h 5 x ± s n = 6 6 x ± s n = 6 A AUC 0 - t B t 1 /2 C T max D C max HPLC-MS 6 HPLC-UV 7-8 HPLC-MS 9

6 2016 Jun Zhu Z Neirinck L. High-performance liquid chroma- tography coupled with negative ion tandem mass spectrometry for determination of pravastatin in human plas- ma J. J Chromatogr B Neuvonen PJ Backman JT Niemi M. Pharmacokinetic comparison of the potential over-the-counter statins 1 2 A 3 F simvastatin lovastatin fluvastatin and pravastatin 7 J. Clin Pharmacokinet J A B C D E F G H J. H1 I J K L M U T nal A Sagirli O. Development of a selective LC method for the determination of pravastatin sodium J. Chromatographia / J Deng S Chen XP Cao D et al. Effects of a concomitant single oral dose of rifampicin on the pharmacoki- netics of pravastatin in a two-phase randomized single-blind placebo-controlled crossover study in healthy Chinese male subjects J. Clin Ther Bauer S Mwinyi J Stoeckle A et al. Quantification of pravastatin in human plasma and urine after solid 7 phase extraction using high performance liquid chromatography with ultraviolet detection J. Chromatogr B T max C max AUC J Keri V Szabo C Arvai EN et al. Novel forms of pravastatin sodium P. WO A Zlatko Pflaum. Crystals of the sodium salt of pravastatin P. AU B SD 14 Jia CY Yin QX Zhang MJ et al. Polymorphic transformation of pravastatin sodium monitored using com- bined online FBRM and PVM J. Org Pro Res Dev ChP M HeFnawy MM MoHaMed MS Abounassif MA et al. High-performance liquid chromatography and derivative spectrophotometry for simultaneous determination of pravastatin and fenofibrate in the dosage form J. Acta Pharm Martín-Islán AP Cruzado MC Asensio R et al. Crystalline polymorphism and molecular structure of sodium pravastatin J. J Phys Chem B Assessment report for Pravafenix. European Medicines Agency Z. Procedure No. EMEA / H / C / J

7 652 Chin J Clin Pharmacol Ther 2016 Jun Clas SD. The importance of characterizing the crystal form of the drug substance during drug development J. Curr Opin Drug Discov Devel A comparative pharmacokinetics study of pravastatin sodium tablets in rats ZHAO Ying 1 ZHANG Na 2 3 PANG Xiaocong 1 SHENG Lisong 1 SONG Junke 1 HE Lan 3 LV Yang 2 DU Guanhua 1 1 Peking Union Medical College Institute of Materia Medica & Chinese Academy of Medical Sciences Beijing Key Laboratory of Drug Targets and Screening Research 2 Peking Union Medical College Institute of Materia Medica & Chinese Academy of Medical Sciences Research Centre of Polymorphic Drugs Beijing Key Laboratory of Polymorphic Drug 3 National Institutes for Food and Drug Control Beijing China ABSTRACT AIM To study the pharmacokinetics of different pravastatin sodium tablets in rats. METHODS An LC-MS method was established for the detection of pravastatin sodium in plasma after a single oral dose of 15 mg /kg pravastatin sodium tablets and a time-plasma concentration curve was presented. Main pharmacokinetic parameters were calculated by DAS Data Processing System. RE- SULTS Determination results of the three bulk drug manufactures indicated that pravastatin form F had a higher absorption and relative bioavailability than form A. Pharmacokinetic parameters of the seven products selected randomly from different industries were different after a single dose of 15 mg / kg pravastatin sodium. Maximum differences of C max T max AUC and t 1 /2 came up to and 1. 4 times. CONCLUSION Polymorphism has an important influence on the differences among the pharmacokinetics of different pravastatin sodium tablets in rats. In addition production process excipient and content of pravastatin sodium should be also considered in the quality control of pravastatin sodium tablets. KEYWORDS pravastatin crystal form pharmacokinetics bioavailability LC-MS 櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂 mm 205 mm 120 CN /R ISSN CSCD IC Ulrichsweb Q cjcpt96@ 163. com http / /www. cjcpt. com

1449 1 相对校正因子的相关方法 1.1 内标多控法研究发现, 在中药各成分间存在着一定的比例关系, 只要各成分的量符合该比例关系, 中药的多 [6] 指标质量控制可以依此法

1449 1 相对校正因子的相关方法 1.1 内标多控法研究发现, 在中药各成分间存在着一定的比例关系, 只要各成分的量符合该比例关系, 中药的多 [6] 指标质量控制可以依此法 1448 相对校正因子在中药多指标测定中的应用研究进展 1, 罗祖良 2, 仇峰 1 1,, 韦日伟 2 1,, 覃禹 2, 张坤 1, 覃洁萍 2, 杨美华 1. 北京协和医学院药用植物研究所, 中草药物质基础与资源利用教育部重点实验室, 北京 100193 2. 广