High‐throughput chiral analysis of albuterol enantiomers in dog plasma using on‐line sample extraction/polar organic mode chiral liquid chromatography with tandem mass spectrometric detection

Abstract

An automated chiral chromatography/tandem mass spectrometry bioanalytical method for the determination of albuterol in dog plasma was developed. The method employed on-line sample extraction using turbulent flow chromatography coupled to a Chirobiotic T column for chiral separation using a polar organic mobile phase consisting of methanol, 0.02% formic acid, and 0.1% ammonium formate. The analytes were detected by a tandem mass spectrometer operated in positive ion mode. The (S)- and (R)-isomers were resolved chromatographically with retention times of 5.1 and 5.6 min, respectively. The analytical run time was 8 min. The enantiomers did not interconvert either in mobile phase or in dog plasma at room temperature over the course of at least 2 h. The assay has a linear dynamic range from 2.5-2500 nM for both enantiomers. The lower limit of quantitation (LLOQ) was 2.5 nM for both enantiomers using 50 microL of plasma. The accuracy and precision of intraday validation were determined at five concentration levels of six replicates. The accuracy of the method for the (R)-isomer ranged from 94-103% of nominal concentrations, and the precision (%CV) ranged from 3.6-12%. The accuracy of the method for the (S)-isomer ranged from 94.5-108% of nominal concentrations, and the precision ranged from 3.2-9.3%. Interday accuracy and precision were evaluated for three days at five concentrations for one replicate. The accuracy of the method for the (R)-isomer ranged from 98-110% of nominal concentrations, and the precision ranged from 1.5-10.6%. The accuracy of the method for the (S)-isomer ranged from 96-104% of nominal concentrations, and the precision ranged from 1.5-8.7%. The combination of turbulent flow on-line sample extraction with polar organic mode chiral chromatography provided a specific, rugged, and high-throughput method for the chiral analysis of albuterol in biological fluids.

Intoxication non létale par la Méthoxétamine : confirmation analytique à l’aide d’un système d’extraction en ligne Turboflow® couplé à de la LC/MS/MS

“…L'autre limite se situe également au niveau de la durée de vie des colonnes d'extraction, mais celles-ci peuvent être préservées par une simple précipitation de l'échantillon biologique en amont de l'extraction en ligne, ce que nous réa-lisons systématiquement dans notre laboratoire. Cette précipi-tation préalable semble ainsi être le meilleur moyen pour allonger la durée de vie des colonnes d'extraction ainsi que le risque d'obstruction [1,18]. Enfin, l'acquisition d'un tel appareillage doit être rigoureusement étudié car relativement coû-teux à l'achat et en consommables et son investissement mé-rite d'être étudié sur le long terme en fonction des demandes adressées au laboratoire.…”

Liquid separation techniques coupled with mass spectrometry for chiral analysis of pharmaceuticals compounds and their metabolites in biological fluids

“…Wu et al [13] used a similar set-up to analyze albuterol enantiomers, a drug used to help asthma patients, in dog plasma. They design a high throughput method with a sample turnout of 8 minutes.…”

Stability-indicating RP-HPLC method for simultaneous estimation of levosalbutamol sulfate and theophylline in combined dosage form

“…Some of the reported methods for racemic salbutamol sulfate includes titrimetric (Basavaiah et al, 2006(Basavaiah et al, , 2007, potentiometric (Abdel-Ghani et al, 2002), spectrophotometric (Basavaiah et al, 2003(Basavaiah et al, , 2006(Basavaiah et al, , 2007Chitlange et al, 2011;Culzoni et al, 2006; Geeta et al ., 1989;Habib et al, 2004;Jain et al, 2011;Mishra et al, 2010;Parimoo et al, 1993;Rathore et al, 1993), spectrofluorimetric (Pandya et al, 2010), HPLC (Bernal et al, 1996;Boulton et al, 1995;Chitlange et al, 2011;Erram et al, 2006;Jain et al, 2011;Kasawar et al, 2010;Kountourellis et al, 1990;Martis et al, 2011;Murtaza et al, 2009;Pai et al, 2009) and LC-MS (Joyce et al, 1998;Wu et al, 2004Wu et al, , 2011Yee et al, 2011). Whereas for levosalbutamol sulfate a few spectrophotometric Thulasama et al, 2009) and HPLC (Ghemud et al, 2012;Halabi et al, 2004; methods are reported.…”