Quantification of fexofenadine in human plasma by liquid chromatography coupled to electrospray tandem mass spectrometry using mosapride as internal standard

Abstract

A rapid high-performance liquid chromatography/positive ion electrospray tandem mass spectrometry method was developed and validated for the quantification of fexofenadine in human plasma using mosapride as internal standard. Following solid-phase extraction, the analytes were separated using an isocratic mobile phase on a reverse-phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M+H]+ ions, m/z 502/466 for fexofenadine and m/z 422/198 for the IS. The method exhibited a linear dynamic range of 1-500 ng/mL for fexofenadine in human plasma. The lower limit of quantification was 1 ng/mL with a relative standard deviation of less than 5% for fexofenadine. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. The total chromatographic run time of 2 min for each sample made it possible to analyze more than 400 human plasma samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic, bioavailability or bioequivalence studies.

Measurement of fexofenadine concentration in micro‐sample human plasma by a rapid and sensitive LC‐MS/MS employing protein precipitation: application to a clinical pharmacokinetic study

“…SPE is a widely adopted method and often achieves clean analytes from biological samples (Robbins et al, 1998;Hofmann et al, 2002;Unoa et al, 2004;Isleyen et al, 2007;Miura et al, 2007;Nirogi et al, 2007;Bharathi et al, 2008;Pathak et al, 2008;Pathak et al, 2008), but the technique is time-consuming and the SPE columns are relatively expensive. In the present work, protein precipitation with methanol was used for the extraction of fexofenadine from human plasma, which produced a clean chromatogram for a drug-free plasma sample and off ered satisfactory absolute recoveries for the analyte.…”

“…Some of these methods (Robbins et al, 1998;Unoa et al, 2004;Miura et al, 2007;Pathak et al, 2008), based on liquid chromatography (LC) using fl uorescence or ultraviolet detection with the lower limit of quantifi cation (LLOQ) at 1-25 ng/mL, have been published. Recently, many methods (Hofmann et al, 2002;Nirogi et al, 2007;Isleyen et al, 2007;Bharathi et al, 2008) using LC-MS with LLOQs at 0.5-3 ng/mL have also been reported, which are much more specifi c and sensitive analytical techniques. In these methods, solid-phase extraction (SPE) and liquid-liquid extraction techniques have been used for handling samples, which has been proven to be an eff ective technique.…”

Extractive Spectrophotometric and Conductometric Methods for Determination of Fexofenadine Hydrochloride in Pharmaceutical Dosage Forms

“…Various spectrophotometric methods have been reported for the determination of fexofenadine hydrochloride [5,[11][12][13][14][15][16][17][18] from its individual and combined formulations with other active ingredients. Fexofenadine has been determined in human plasma by HPLC with UV detection [19], fluorescence detection [20] and tandem mass spectrometry detection [21][22][23].…”

Changing need for bioanalysis during drug development

“…Over the past few decades, a plethora of assays has been continuously developed for new chemical entities (NCEs) to support various stages of discovery and development, including assays for important metabolites (Satonin et al, 2007;Zeng et al, 2007;He et al, 2007;Chawla et al, 2006). Additionally, multiple analytical procedures are available for prescription medicines (Rx) and/or generic products (Basha et al, 2007;Link et al, 2007;Oostendorp et al, 2007;Kiel et al, 2007;Wang et al, 2006;Dotsikas et al, 2007;Nirogi et al, 2007;Venkatesh et al, 2006;Pavan Kumar et al, 2006;Pasha et al, 2006). Needless to say, all of the above document the importance of bioanalytical aspects not only during discovery and development of NCEs but also during the post approval period.…”