Determination of lansoprazole enantiomers in dog plasma by column‐switching liquid chromatography with tandem mass spectrometry and its application to a preclinical pharmacokinetic study

Abstract

Lansoprazole, a selective proton pump inhibitor, has a chiral benzimidazole sulfoxide structure and is used for the treatment of gastric acid hypersecretory related diseases. To investigate its stereoselective pharmacokinetics, a column-switching liquid chromatography with tandem mass spectrometry method was developed for the determination of lansoprazole enantiomers in dog plasma using (+)-pantoprazole as an internal standard. After a simple protein precipitation procedure with acetonitrile, matrix components left behind after sample preparation were further eliminated from the sample by reversed-phase chromatography on a C18 column. The fluent was fed to a chiral column for the separation of lansoprazole enantiomers. Baseline separation of lansoprazole enantiomers was achieved on a Chiralcel OZ-RH column using acetonitrile/0.1% formic acid in water (35:65, v/v) as the mobile phase at 40°C. The linearity of the calibration curves ranged from 3 to 800 ng/mL for each enantiomer. Intra- and inter-day precisions ranged from 2.1 to 7.3% with an accuracy of ±1.7% for (+)-lansoprazole, and from 1.6 to 6.9% with an accuracy of ±3.5% for (-)-lansoprazole, respectively. The validated method was successfully applied for the stereoselective pharmacokinetic study of lansoprazole in beagle dog after intravenous infusion.

Forced degradation studies of lansoprazole using LC‐ESI HRMS and 1H‐NMR experiments: in vitro toxicity evaluation of major degradation products

“…Finally, the mobile phase with a combination of 10 mM ammonium acetate and ACN gives better separation and good peak shape for lansoprazole and its degradation products (DP 1-8). The linear gradient program is as follows: (Tmin/% proportion of solvent B): 0-5 /10, 5-7 /30, 7-14 /40, [14][15][16][17][18][19][20] /45, 20-30 /45, [30][31][32][33][34][35] /50, 35-37 /70, 37-38 /10, 38-40 /10. The column temperature, flow rate, injection volume and detector wavelength were at 30°C, 1.0 ml/min, 20.0 μl and 285 nm, respectively.…”

“…It is used to treat and prevent ulcer, Zollinger-Ellison syndrome and erosive esophagitis. Few HPLC methods have been reported for the determination of lansoprazole in plasma [15,16] and quantification of (R)-(+)-and (S)-(À)-lansoprazole enantiomers and related impurities. [17] Few studies have been reported on the characterization of acidic [18] and hydrolytic degradation products.…”

Enantioselective analysis of lansoprazole in rat plasma by LC–MS/MS: Application to a stereoselective pharmacokinetic study

“…As a consequence of the numerous merits of R-(+)-lansoprazole, such as the slower metabolism, higher plasma concentration, longer elimination half-time and greater systemic exposure, it was developed and approved for marketing as a novel proton-pump inhibitor with the trade name Dexilant in 2009 (Gomes, Cassiano, Pedrazzoli, & Cass, 2010;Hershcovici, Jha, & Fass, 2011;Katsuki, Hamada, Nakamura, Arimori, & Nakano, 2001;Metz, Vakily, & Dixit, 2009). Wang et al reported a column-switching LC-MS/MS method for the quantification of lansoprazole enantiomers in dog plasma, while the column-switching procedure required complicated and specific equipment (Wang et al, 2015). Additionally, the sample extraction of those methods was not ideal for high-throughput bioanalysis.…”

“…LC-MS/MS has became increasingly prevalent in biochemical analysis owing to its better sensitivity and selectivity, and its ability to provide high sample throughput (De et al, 2010;Wang et al, 2014). Wang et al reported a column-switching LC-MS/MS method for the quantification of lansoprazole enantiomers in dog plasma, while the column-switching procedure required complicated and specific equipment (Wang et al, 2015). In addition, it is still unclear whether or not the chiral switch between R-(+)-and S-(−)-lansoprazole in rat plasma samples exists, and the pharmacokinetics of dexlansoprazole and racemic lansoprazole after oral administration in rat have not been compared.…”

Enantioselective determination of (R)‐ and (S)‐lansoprazole in human plasma by chiral liquid chromatography with mass spectrometry and its application to a stereoselective pharmacokinetic study

“…Wang et al. reported a column‐switching LC–MS/MS method for the determination of lansoprazole enantiomers in dog plasma. However, the column‐switching procedure required specific equipment and this method was not validated for human pharmacokinetic study.…”