Development and validation of a capillary electrophoresis method for determination of enantiomeric purity and related substances of esomeprazole in raw material and pellets

Abstract

A capillary electrophoresis method using CDs for quality control of esomeprazole (ESO) in terms of enantiomeric purity and related substances in raw material and pellets was developed. ESO is the S-enantiomer of omeprazole (OMZ). Several parameters were evaluated, including type and concentration of buffer and CD, concentration of additives and electrolyte pH. Resolution between the enantiomers of OMZ obtained for each parameter tested was calculated and the presence of the main related substance such as OMZ sulfone was carefully monitored. The optimized system consisted of 100 mM Tris-phosphate buffer pH 2.5 with 20 mM 2-hydroxypropyl-β-CD, 1 mM sodium dithionite, temperature at 15°C, voltage at 28 kV, and UV detection at 301 nm. Once optimized, the electrophoretic system was validated according to ICH guidelines. The limits of detection and quantification for R-OMZ were 0.6 μg/mL (0.06% w/w of ESO) and 2.0 μg/mL (0.2% w/w of ESO), respectively. A mean concentration of R-OMZ <0.2% limit established by the United States Pharmacopeia (USP) was found in the raw material and six-pellet samples of ESO. No other impurities were found in the samples under these conditions. Therefore, the developed method was found to be appropriate not only for enantiomeric quality control of ESO but also for the analysis of ESO and the main related substance in raw material and pharmaceutical formulations as well as for stability indicating studies.

Chiral Separation of the Enantiomers of Omeprazole and Pantoprazole by Capillary Electrophoresis

“…According to previous work, sodium disulfide (5 mM) or sodium dithionite (1 mM) can be used as antioxidants to prevent degradation of omeprazole under acidic conditions [11,13]. Omeprazole was almost 50 % degraded in 24 h, although in the first 4 h after sample preparation degradation was <5 %; we therefore analyzed omeprazole under acidic conditions immediately after dissolution of the analyte.…”

“…The enantiomers of omeprazole and its metabolite 5-hydroxyomeprazole have been separated by non-aqueous CE with heptakis-(2,3-di-O-methyl-6-O-sulfo)-β-CD as chiral selector in ammonium acetate buffer acidified with formic acid in methanol [12]. A validated method for combined analysis of the enantiomeric purity of both esomeprazole and related substances was based on use of Tris-phosphate buffer and 2-hydroxypropyl-β-CD as chiral selector [13]. Chiral separation of pantoprazole has been achieved by CE with a mixed borate-phosphate buffer at neutral pH and with sulfated-β-CD as chiral selector, but with the disadvantage of long migration time [14].…”

Recent advances in capillary electrophoretic migration techniques for pharmaceutical analysis (2013–2015)

“…Recent publications on the analysis of related substances in pharmaceutical drugs have been compiled in Table 1 [39,40,42,43,45,[62][63][64][65][66][67][68][69][70][71][72]. Most separations were carried out in the CZE mode, while four methods applied MEKC [42,65,69,70] and one MEEKC conditions [40].…”

Development and validation of a micellar electrokinetic capillary chromatography method for the determination of goserelin and related substances

“…The efficiency at separating peptides 1, 5, and 6 was decreased at pH of less than 4.0 due to the strong electrostatic repulsion between positively charged micelles and cationic analytes at low pH [20,22]. Good resolution was obtained at pH 4.2 because of the low magnitude of the EOF, which allowed appreciable differentiation between the electrophoretic mobility of all peptides [26]. At pH 4.4-4.6, the peak shapes obtained for peptides 8 and 9 were obviously poor, and the signal response was low.…”