Abstract
A simple HPLC-DAD method using a reverse phase column and isocratic elution for the simultaneous determination of omeprazole (OME), 5-hydroxyomeprazole (HOME) and omeprazole sulphone (OMES) was developed. The proposed method was used to study CYP2C19 and CYP3A4 genetic polymorphisms using OME as the probe drug in a group of Brazilian volunteers. OME, HOME and OMES were extracted from plasma samples with Tris buffer pH 9.5 (0.2 mol L-1) and ethyl acetate. HPLC separation was achieved using a Shim-Pack RP-18e (150 ´ 4.6 mm i.d., 5 µm) column, with acetonitrile phosphate buffer pH 7.6 (24:76) as mobile phase and total run time of 15 min. Retention times were 2.7 min for internal standard (sulpiride), 4.1 min for HOME, 11.6 min for OME and 12.6 min for OMES. Detection (UV at 302 nm) of analytes was linear in the range from 25 to 1000 ng mL-1. Extraction recoveries were in the range of 64.3 to 73.2% for all analytes. A group of 38 Brazilian healthy volunteers was phenotyped with this method, after a single oral dose of 20 mg omeprazole. The method presented adequate accuracy and precision, with limit of quantification of 25 ng mL-1 for omeprazole and metabolites, which allowed the identification of ultra-rapid metabolizers for both CYP2C19 and CYP3A4 and took advantage of the selective identification offered by diode-array detectors.
Highlights
Omeprazole (OME), a substituted α-pyridylmethylsulfinylbenzimidazole, is a gastric H+, K+, ATPase inhibitor
Omeprazole is administered as a racemic mixture and presents enantioselective metabolism, with the (R)-(+)-omeprazole being mainly hydroxylated by CYP2C19 and (S)-(–)-omeprazole being preferentially metabolized to the sulfone by the CYP3A4.6–8 OME is rapidly removed from plasma, with an estimated half-life of about 2 h
Increased proportion of acetonitrile did not allow the separation of internal standard and HOME from early eluting matrix constituents and increased percentage of phosphate buffer led to unacceptable high retention times
Summary
Omeprazole (OME), a substituted α-pyridylmethylsulfinylbenzimidazole, is a gastric H+, K+, ATPase inhibitor. OME has been widely used as a potent inhibitor. Simultaneous Determination of Omeprazole, Hydroxyomeprazole and Omeprazole. Omeprazole sulfone (OMES).[1,2,3,4] It is well established that CYP2C19 is the major enzyme in the formation of HOME, and CYP3A4 is mainly involved in the production of OMES (Figure 1).[5] Omeprazole is administered as a racemic mixture and presents enantioselective metabolism, with the (R)-(+)-omeprazole being mainly hydroxylated by CYP2C19 and (S)-(–)-omeprazole being preferentially metabolized to the sulfone by the CYP3A4.6–8 OME is rapidly removed from plasma, with an estimated half-life of about 2 h.1
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