Chilton A S, Godward R E, Carey P F
Glaxo Research and Development Ltd, Ware, Herts, UK.
J Pharm Biomed Anal. 1995 Feb;13(2):165-9. doi: 10.1016/0731-7085(94)00122-i.
The clinical development of salmeterol xinafoate, the 1-hydroxy-2-naphthoic acid salt of salmeterol, a potent long acting beta 2 agonist bronchodilator, has required the development of a method for the determination of 1-hydroxy-2-naphthoic acid (HNA), in human plasma. A sensitive, accurate and precise method was, therefore, required to enable the pharmacokinetic profile to be established. HNA was determined in human plasma using a semi-automated procedure with solid-phase extraction using an automated analytical sample processor (AASP) and high-performance liquid chromatography (HPLC) with fluorescence detection. The method was sensitive to 10 ng ml-1. The method is specific for HNA with respect to endogenous plasma components and has been shown to be robust, accurate and precise. Over four independent assay runs, the relative standard deviations (RSD) of the quality control samples (QC) were 1.6, 2.4 and 5.5% at 180, 100 and 40 ng ml-1, respectively. A pharmacokinetic profile of HNA in man has been established from a single dose kinetic study in healthy volunteers following an oral dose of 500 micrograms salmeterol xinafoate, equivalent to 225 micrograms HNA. Maximum plasma concentrations attained at 1 h after dosing ranged between 35.3 and 66.8 ng ml-1 and were within the calibration range of the assay.
沙美特罗昔萘酸盐（沙美特罗的1-羟基-2-萘甲酸盐，一种强效长效β2激动剂支气管扩张剂）的临床开发需要建立一种测定人血浆中1-羟基-2-萘甲酸（HNA）的方法。因此，需要一种灵敏、准确且精密的方法来建立药代动力学特征。使用自动分析样品处理器（AASP）进行固相萃取并结合高效液相色谱（HPLC）和荧光检测的半自动程序来测定人血浆中的HNA。该方法对10 ng/ml的HNA敏感。相对于内源性血浆成分，该方法对HNA具有特异性，并且已证明具有稳健性、准确性和精密性。在四次独立的分析运行中，质量控制样品（QC）在180、100和40 ng/ml时的相对标准偏差（RSD）分别为1.6%、2.4%和5.5%。在健康志愿者口服500微克沙美特罗昔萘酸盐（相当于225微克HNA）后的单剂量动力学研究中，已建立了HNA在人体中的药代动力学特征。给药后1小时达到的最大血浆浓度在35.3至66.8 ng/ml之间，且在该分析的校准范围内。
