The quantification of paracetamol, paracetamol glucuronide and paracetamol sulphate in plasma and urine using a single high-performance liquid chromatography assay

The quantification of paracetamol, paracetamol glucuronide and paracetamol sulphate in plasma and urine using a single high-performance liquid chromatography assay
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DOI:
10.1016/s0731-7085(03)00573-9
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发表时间:
2004-02-18
影响因子:
3.4
通讯作者:
Evans, AM
Evans, AM
中科院分区:
医学3区
文献类型:
--
作者:
Jensen, LS;Valentine, J;Evans, AM

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生物体液中扑热息痛的测定有多种分析方法。然而,为了了解扑热息痛的命运以及其他药物对其体内处置的影响,需要对尿液和血浆中的主要代谢物进行定量。因此,需要一种同时定量血浆和尿液中的对乙酰氨基酚、对乙酰氨基酚葡萄糖醛酸(PG)和硫酸对乙酰氨基酚(PS)的方法,具有更高的灵敏度,特别是在可用血浆容量较低的情况下。建立了一种简便的等规反相液相色谱分光光度分析方法。方法采用反相C18柱,检测波长为254 nm,流动相为正磷酸二氢钾(0.1M)-异丙醇-四氢呋喃(100:1.5:0.1,v/v/v),用磷酸调节pH至3.7。该方法对扑热息痛、PG和PS的血药浓度在0.4~200微米范围内线性关系良好。用于尿液中的PG和PS。该方法在100~20000微米的浓度范围内具有良好的线性关系。在这些范围内,准确度和精密度都低于12%。该方法已用于测定手指点样采集的血浆中扑热息痛和两种代谢物的浓度,以及单剂量口服1000毫克扑热息痛的健康志愿者尿液中的代谢物浓度。(C)2003爱思唯尔B.V.保留所有权利。
A range of analytical methods exist for the determination of paracetamol in biological fluids. However, to understand the fate of paracetamol and the effect of other drugs on its disposition in vivo, the major metabolites require quantification in urine and plasma. A method to simultaneously quantify paracetamol, paracetamol glucuronide (PG) and paracetamol sulphate (PS) in plasma and urine with superior sensitivity is therefore desired, especially if the volume of plasma available is low. A simple isocratic reverse phase high-performance liquid chromatography (HPLC) assay with spectrophotometric detection has been developed. The method, requiring only 100 mul of plasma and 50mul of urine, utilizes a reversed-phase C 18 column, a wavelength of 254 nm for detection and a mobile phase composed of potassium dihydrogen orthophosphate (0.1 M)-isopropanol-tetrahydrofuran (THF) (100: 1.5:0.1, v/v/v) adjusted to pH 3.7 with phosphoric acid. The method is sensitive and linear in plasma within a concentration range from 0.4 to 200 muM for paracetamol, PG and PS. For PG and PS in urine. the method is sensitive and linear within a concentration range from 100 to 20,000 muM. Over these ranges, accuracy and precision were less than 12%. The assay has been used to measure concentrations of paracetamol and the two metabolites in plasma collected by finger-prick sampling and of the metabolites in urine from healthy volunteers administered a single oral dose of 1000 mg of paracetamol. (C) 2003 Elsevier B.V. All rights reserved.