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一种同时测定生物流体中乙酰水杨酸、水杨酸和水杨尿酸的高灵敏度高效液相色谱法:药代动力学、代谢及监测意义

A highly sensitive HPLC method for the simultaneous determination of acetylsalicylic, salicylic and salicyluric acids in biologic fluids: pharmacokinetic, metabolic and monitoring implications.

作者信息

Krivosíková Z, Spustová V, Dzúrik R

机构信息

Institute of Preventive and Clinical Medicine, Bratislava, Slovakia.

出版信息

Methods Find Exp Clin Pharmacol. 1996 Oct;18(8):527-32.

PMID:9044241
Abstract

A number of methods have been developed for the determination of acetylsalicylic acid (ASA, aspirin). However, they are not sensitive enough for the simultaneous determination of ASA and its major metabolites salicylic (SA) and salicyluric (SUA) acids at the low dosage schedules (30-100 mg ASA/d). The HPLC method with UV detection described here fulfills these requirements. The calibration curves were linear at the range 0.18-10 mumol/l. Coefficients of variation were 3.9% for SUA, 7.89% for ASA and 5.88% for SA. The recovery of ASA, SA and SUA was between 90-105%. ASA administered in doses of 30-400 mg was rapidly absorbed from gastrointestinal tract and deacetylated, forming the dominant plasma metabolite SA. SA was eliminated to about 60% by conjugation with glycine and therefore SUA was a dominant metabolite in urine. ASA was never found in urine at the low-dose ASA treatment. For this reason, SUA, but not ASA, can be determined in urine and may be used for monitoring patient compliance.

摘要

已经开发出多种测定乙酰水杨酸(ASA,阿司匹林)的方法。然而,在低剂量方案(30 - 100毫克ASA/天)下,它们对于同时测定ASA及其主要代谢物水杨酸(SA)和水杨尿酸(SUA)的灵敏度不够。本文所述的带紫外检测的高效液相色谱法满足了这些要求。校准曲线在0.18 - 10微摩尔/升范围内呈线性。SUA的变异系数为3.9%,ASA为7.89%,SA为5.88%。ASA、SA和SUA的回收率在90 - 105%之间。以30 - 400毫克剂量给药的ASA迅速从胃肠道吸收并脱乙酰化,形成主要的血浆代谢物SA。SA约60%通过与甘氨酸结合而消除,因此SUA是尿液中的主要代谢物。在低剂量ASA治疗时,尿液中从未发现过ASA。因此,可以在尿液中测定SUA而非ASA,并且可用于监测患者的依从性。

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