Determination and Pharmacokinetics of Omeprazole Enantiomers in Human Plasma and Oral Fluid Utilizing Microextraction by Packed Sorbent and Liquid Chromatography-Tandem Mass Spectrometry.

Hytham Ahmed,Hatem Elmongy,Hirsh Koyi,Eva Branden,Abdel-Aziz Wahbi,Mohamed Abdel-Rehim,Ahmad Amini,Eladia M Pena Mendez

doi:10.1155/2021/8845139

Abstract

In the present work, the determination of omeprazole (OME) enantiomers in oral fluid and plasma samples was carried out utilizing microextraction by packed sorbent (MEPS) and liquid chromatography-tandem mass spectrometry. A chiral column with cellulose-SB phase was used for the first time for enantiomeric separation of OME with an isocratic elution system using 0.2% ammonium hydroxide in hexane-ethanol mixture (70 : 30, v/v) as the mobile phase. OME enantiomers were determined utilizing a triple quadrupole tandem mass spectrometer in positive ion mode (ESI+) monitoring mass transitions: m/z 346.3 ⟶ 198.0 for OME and m/z 369.98 ⟶ 252.0 for internal standard. The limits of detection and quantification of the present method for both enantiomers were 0.1 and 0.4 ng/mL, respectively. The method validation provided good accuracy and precision. The matrix effect factor was less than 5%, and no interfering peaks were observed. The interday precision values ranged from 2.2 to 7.5 (%RSD), and the accuracy of determinations varied from −9.9% to 8.3%. In addition, the pharmacokinetics (PK) of omeprazole enantiomers in healthy subjects after a single oral dose was investigated. (S)-Enantiomers showed higher levels than (R)-enantiomers throughout 24 h. It was found that the mean maximum concentrations of (R)- and (S)-omeprazole in plasma samples were about two times higher than in oral fluid.

Highlights

Omeprazole (OME) is the first proton pump inhibitor (PPI) that acts by blocking the H+- K + ATPase enzymes irreversibly
The pharmacodynamics and pharmacokinetics (PK) of a chiral drug are potentially different between the optical isomers
A new method based on liquid chromatography system (LC)-MS/MS has been developed and validated for the assay of the enantiomers of OME in human plasma and oral fluid samples

Summary

Introduction

Omeprazole (OME) is the first proton pump inhibitor (PPI) that acts by blocking the H+- K + ATPase enzymes (proton pumps) irreversibly. OME is indicated in treatment of all acid-related diseases, where the target of treatment is to reduce gastric acid secretion, such as dyspepsia, peptic ulcer, gastric ulcer, and gastroesophageal reflux disease [1]. It is a chiral drug but used as a racemic mixture and pure enantiomer for medicinal purposes [2]. The pharmacodynamics and pharmacokinetics (PK) of a chiral drug are potentially different between the optical isomers. Erefore, it is important to study the individual enantiomers to get clear knowledge about pharmacokinetics and pharmacodynamics of any chiral drug.

Methods

Findings

Discussion

Conclusion