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用于检测晶状体和血浆中醛糖还原酶抑制剂依米司他的毛细管气相色谱-电子捕获分析法

Capillary gas chromatographic-electron-capture assay for the aldose reductase inhibitor imirestat in lens and plasma.

作者信息

McCue B A, Park Y H, Brazzell R K, Boltralik J J

机构信息

Research and Development, Alcon Laboratories, Inc., Fort Worth, TX 76134.

出版信息

J Chromatogr. 1991 Apr 19;565(1-2):255-64. doi: 10.1016/0378-4347(91)80388-s.

DOI:10.1016/0378-4347(91)80388-s
PMID:1908477
Abstract

A sensitive and selective gas chromatographic-electron-capture assay was developed for the determination of the aldose reductase inhibitor imirestat in lens and plasma. The method involves solid-phase extraction of drug and internal standard from the plasma specimen or lens sample homogenate using "Baker"-10 SPE extraction columns followed by derivatization with pentafluorobenzyl bromide and further purification. Derivatives of drug and internal standard were separated on a fused-silica capillary column and analyzed using a 63Ni electron-capture detector. The limit of detection was 2.5 ng per lens or ml of plasma. The method was used to evaluate the pharmacokinetics of imirestat in human subjects and to quantitate imirestat in animal lens tissue following topical ocular administration.

摘要

开发了一种灵敏且具选择性的气相色谱 - 电子捕获分析法,用于测定晶状体和血浆中的醛糖还原酶抑制剂依米司他。该方法包括使用“贝克” - 10固相萃取柱从血浆标本或晶状体样品匀浆中固相萃取药物和内标,随后用五氟苄基溴进行衍生化并进一步纯化。药物和内标的衍生物在熔融石英毛细管柱上分离,并用63Ni电子捕获检测器进行分析。检测限为每个晶状体或每毫升血浆2.5纳克。该方法用于评估依米司他在人体受试者中的药代动力学,并在局部眼部给药后对动物晶状体组织中的依米司他进行定量。

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Capillary gas chromatographic-electron-capture assay for the aldose reductase inhibitor imirestat in lens and plasma.用于检测晶状体和血浆中醛糖还原酶抑制剂依米司他的毛细管气相色谱-电子捕获分析法
J Chromatogr. 1991 Apr 19;565(1-2):255-64. doi: 10.1016/0378-4347(91)80388-s.
2
Pharmacokinetics of the aldose reductase inhibitor imirestat following topical ocular administration.局部眼部给药后醛糖还原酶抑制剂依米司他的药代动力学
Pharm Res. 1990 Feb;7(2):192-8. doi: 10.1023/a:1015893122054.
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Determination of AL01576 concentration in rat lenses and plasma by bioassay for aldose reductase activity measurements.通过生物测定法测定大鼠晶状体和血浆中AL01576的浓度以进行醛糖还原酶活性测量。
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Saturable tissue binding and imirestat pharmacokinetics in rats.大鼠体内的饱和组织结合与依米司他的药代动力学
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Dose-dependent pharmacokinetics of the aldose reductase inhibitor imirestat in man.醛糖还原酶抑制剂依米司他在人体中的剂量依赖性药代动力学。
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Application of 19F-n.m.r. spectroscopy to the identification of dog urinary metabolites of imirestat, a spirohydantoin aldose reductase inhibitor.
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Determination of aldose reductase activity in the eye by localized magnetic resonance spectroscopy.通过局部磁共振波谱法测定眼中醛糖还原酶的活性。
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Minimal effects of two aldose reductase inhibitors, AL-1576 and AL-4114, after subacute topical-ocular dosing on xenobiotic biotransformation in rabbits.
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Comparison of the pharmacokinetics and pharmacodynamics of the aldose reductase inhibitors, AL03152 (RS), AL03802 (R), and AL03803 (S).醛糖还原酶抑制剂AL03152(RS)、AL03802(R)和AL03803(S)的药代动力学和药效学比较。
Pharm Res. 1993 Apr;10(4):593-7. doi: 10.1023/a:1018962405911.