RESUMEN
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.
