Preparation of Optically Pure Esomeprazole and Its Related Salt

Raju, S. V. N.; Purandhar, Koilkonda; Reddy, Padi Pratap; Reddy, G. Madhusudhan; Reddy, Lekkala Amarnath; Reddy, Kikkuri Srirami; Sreenath, K.; Mukkanti, K.; Reddy, Ganji Santhi

doi:10.1021/op049779d

Cited by 12 publications

(5 citation statements)

References 6 publications

(6 reference statements)

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“…Racemic omeprazole was purchased from Sigma-Aldrich (St. Louis, MO). Separation of the omeprazole enantiomers was performed according to published methods (Raju et al, 2006). All other chemicals used were purchased from Sigma-Aldrich and were of the highest purity available.…”

Section: Methodsmentioning

confidence: 99%

CYP2C19 Inhibition: The Impact of Substrate Probe Selection on in Vitro Inhibition Profiles

Foti¹,

Wahlstrom²

2007

Drug Metab Dispos

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ABSTRACT:Understanding the potential for cytochrome P450 (P450)-mediated drug-drug interactions is a critical part of the drug discovery process. Factors such as nonspecific binding, atypical kinetics, poor effector solubility, and varying ratios of accessory proteins may alter the kinetic behavior of an enzyme and subsequently confound the extrapolation of in vitro data to the human situation. The architecture of the P450 active site and the presence of multiple binding regions within the active site may also confound in vitro-in vivo extrapolation, as inhibition profiles may be dependent on a specific inhibitor-substrate interaction. In these studies, the inhibition profiles of a set of 24 inhibitors were paneled against the CYP2C19 substrate probes ( The cytochrome P450 superfamily of drug-metabolizing enzymes is involved in the metabolism of the majority of currently prescribed drugs and new chemical entities. Within the P450 superfamily, members of the human CYP2C family (CYP2C8, CYP2C9, CYP2C18, and CYP2C19) are responsible for the metabolism of approximately 20% of marketed drugs (Goldstein, 2001). Of the four clinically relevant CYP2C isoforms noted above, CYP2C9 and CYP2C19 are the most highly conserved, with approximately 91% structural similarity between the two enzymes (Romkes et al., 1991). There is roughly 80% sequence identity among all four CYP2C isoforms (Ridderström et al., 2001). Crystal structures have been published for CYP2C8 and CYP2C9 (Williams et al., 2003;Schoch et al., 2004), although currently only homology models exist for CYP2C18 and CYP2C19 (Ridderström et al., 2001;Suzuki et al., 2004).CYP2C19 is a polymorphic enzyme that accounts for less than 5% of hepatic P450 (Ring et al., 2001) and 2 to 3% of intestinal P450 content (Paine et al., 2006). The CYP2C19 poor metabolizer phenotype is found in approximately 25% of Asians and only 3 to 5% of Caucasians (Rodrigues and Rushmore, 2002). Commonly used drugs that are metabolized by CYP2C19 include proton pump inhibitors such as omeprazole and lansoprazole, psychotropic drugs including diazepam and imipramine, and anticonvulsants such as phenobarbital and mephenytoin. Unlike CYP2D6, another polymorphic drug-metabolizing enzyme, CYP2C19, has also been shown to be inducible by both rifampicin and dexamethasone.In drug discovery, phenotyping new chemical entities for CYP2C19-mediated metabolism as well as for their potential to inhibit CYP2C19 is a common practice because of the potential liabilities of the CYP2C19 polymorphism. In vitro assays to examine drug-drug interactions (DDIs) commonly use (S)-mephenytoin as a probe substrate for CYP2C19-catalyzed reactions, although difficulties can arise from the relatively low rate of turnover to its 4Ј-hydroxy metabolite. According to recent U.S. Food and Drug Administration guidance (http://www.fda.gov/cder/drug/ druginteractions/default.htm), alternative metabolic pathways that can be used as probes of CYP2C19 activity in vitro include omeprazole metabolism to 5-hydroxyomeprazole and the format...

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Section: Methodsmentioning

confidence: 99%

CYP2C19 Inhibition: The Impact of Substrate Probe Selection on in Vitro Inhibition Profiles

Foti¹,

Wahlstrom²

2007

Drug Metab Dispos

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“…This Esomeprazole magnesium (Fig. 2) is a proton pump inhibitor chemically designated as bis(5-methoxy-2-[(S)-[(4-methoxy-3,5-dimethyl-2-pyridinyl) methyl]sulfinyl]-1H-benzimidazole-1-yl) magnesium trihydrate [9][10]. It is an optical isomer used for acid related diseases [11].…”

Section: Preparation Of Standard Solutionsmentioning

confidence: 99%

Development and Validation of Liquid Chromatographic Method for Naproxen and Esomeprazole in Binary Combination

Razzaq

Ashfaq

Khan

et al. 2012

J. Chil. Chem. Soc.

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The present study reports the development and validation of a simple, economic and sensitive HPLC method for the concurrent determination of naproxen and esomeprazole in pharmaceutical formulations. Isocratic chromatography was performed with C-18 column and mixture of phosphate buffer (pH 6.1) and acetonitrile in ratio of (40:60, v/v) at 1.5 mlmin -1. The eluents were monitored at 302 nm using UV detector. The method was isocratic in the range of 9.38 to 300 µgml -1 for naproxen and 0.5 to 16 µgml -1 for esomeprazole. Validation of the method was performed by testing parameters like linearity, accuracy, precision, robustness, specificity, LOD and LOQ values. In the specificity the drugs were subjected to forced degradation studies like acidic, basic, oxidative and thermal stresses. Both the analytes were separated within three minutes. As the method separates the degradation products produced during forced degradation studies from the active analytes so it can be used not only for regular determination of naproxen and esomeprazole but also for their stability studies.Key words: HPLC, acetonitrile, isocratic, specificity, forced degradation study.e-mail: ashfaqchemist@hotmail.com 1-INTRODUCTIONNaproxen (Fig.1) chemically designated as [(S)-6-methoxy-alpha-methyl-2-naphthaleneacetic acid] is non-steroidal anti-inflammatory medicine that demonstrates both antipyretic and analgesic behavior [1][2][3][4]. It can be used for the remedy of various diseases, such as rheumatoid arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, primary dysmenorrheal and acute gout [5]. After taken orally, naproxen is partially metabolized to its 6-O-desmethylated active metabolite. Both the drug and its metabolite are then excreted through urine either as unchanged or in conjugation with sulphate or glucoronic acid [6][7][8].A careful literature survey did not reveal any single analytical technique for the determination of naproxen and esomeprazole simultaneously. Therefore, attempts were made to develop and validate an isocratic reverse phase HPLC method to determine both drugs simultaneously. We are currently engaged in binary combination analysis of different classes of drugs in synthetic mixtures and in pharmaceutical formulations [30][31][32][33][34][35][36][37][38][39]. The present work is therefore, aimed to attain the optimum chromatographic conditions for the determination of naproxen and esomeprazole simultaneously.We describe in this paper a simple, cheap, sensitive and validated HPLC method with run time less than 3 minutes for the determination of naproxen and esomeprazole simultaneously in pharmaceutical formulations. The developed method can be applied to routine quality control analysis of drugs and for other analytical purposes. 2-EXPERIMENTAL Chemicals and ReagentsReference standards of both naproxen and esomeprazole with claimed percentage purity of 99.62 and 99.71 % respectively were kindly gifted by Schazoo Zaka Laboratories (Lahore, Pakistan). Acetonitrile (chromatography grad...

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“…Nexium, the magnesium salt of S -omeprazole, was one such prazole developed by AstraZeneca and used for the treatment of acid-related diseases . Earlier we have reported a resolution process for the synthesis of the magnesium salt of S -omeprazole through a transition metal complex using a combination of d -(−)-diethyl tartrate, Ti(O i Pr) 4 , and l -(+)-mandelic acid as resolving agents . Herein we wish to report our systematic investigation on the significant role of water, temperature, and the mole ratio of the resolving agents in the resolution of omeprazole sodium.…”

Section: Introductionmentioning

confidence: 99%

“…5 Earlier we have reported a resolution process for the synthesis of the magnesium salt of S-omeprazole through a transition metal complex using a combination of D-(-)-diethyl tartrate, Ti(O i Pr) 4 , and L-(+)-mandelic acid as resolving agents. 6 Herein we wish to report our systematic investigation on the significant role of water, temperature, and the mole ratio of the resolving agents in the resolution of omeprazole sodium. Though the influence of water and temperature in asymmetric sulfoxidation is well precedent in the literature, 7 the effect of these parameters on the resolution of sulfoxides is not yet explored.…”

Section: Introductionmentioning

confidence: 99%

An Investigation on Key Parameters That Influence the Resolution of Omeprazole Sodium

Reddy

Malakondaiah

Babu

et al. 2007

Org. Process Res. Dev.

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Preparation of Optically Pure Esomeprazole and Its Related Salt

Cited by 12 publications

References 6 publications

CYP2C19 Inhibition: The Impact of Substrate Probe Selection on in Vitro Inhibition Profiles

CYP2C19 Inhibition: The Impact of Substrate Probe Selection on in Vitro Inhibition Profiles

Development and Validation of Liquid Chromatographic Method for Naproxen and Esomeprazole in Binary Combination

An Investigation on Key Parameters That Influence the Resolution of Omeprazole Sodium

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