Omeprazole Formulations Research Articles

Novel omeprazole delayed release orally disintegrating tablets for enhanced patient compliance: a case of model informed formulation development

The advanced in silico simulation tools, such as physiologically based biopharmaceutics models (PBBM) or physiologically based pharmacokinetic models (PBPK), play critical role in model informed formulation development. This approach has been successfully implemented in the present case for development of novel omeprazole delayed-release orally disintegrating tablets (ODT) formulation, aimed to enhance patient compliance. PBBM was developed using physicochemical, biopharmaceutical, and dissolution data. The dissolution studies for pilot formulations were conducted in biopredictive media in fasting (0.1 N HCl followed by pH 6.8) and fed (pH 5 followed by pH 6.8) conditions. The model was extensively validated in three stages: pilot fasted, pilot fed virtual bioequivalence and food effect assessments. Impressively, the model was able to predict both passed and failed batches appropriately. Based on insights from the pilot study, a higher scale pivotal formulation was optimised. Prospective predictions were made for pivotal formulations using validated model and bio results were found to be in line with model predictions in fasting condition. Overall, a rationale and patient compliant formulation was developed using innovative modelling approach and filed to regulatory agency. The novel omeprazole formulation enhanced patient compliance through ease of administration thereby circumventing challenges of conventional formulation.

Application of Galenic Strategies for Developing Gastro-Resistant Omeprazole Formulation for Pediatrics.

This study addresses a critical need in pediatric pharmacotherapy by focusing on the development of an enteric formulation of omeprazole for pediatric use. Omeprazole, a widely used proton pump inhibitor, is essential for treating various gastrointestinal disorders in children. The main objective is to design a compounding formula that can be prepared in hospital pharmacy services without the need for industrial equipment, which is often unavailable in these settings. The research applied different galenic strategies to overcome the challenges of omeprazole's instability in acidic environments and its complex pharmacokinetic and physicochemical properties. The experiments were conducted sequentially, employing salting out, ionic gelation, and matrix granulation strategies. Based on the results obtained, the control conditions and parameters for the various trials were established. Among the techniques used, wet granulation proved to be the most promising, achieving a gastro-resistance level of 44%. In contrast, the ionic gelation and salting-out techniques did not yield satisfactory results. The findings of this study underscore the need to adopt alternative formulation strategies to ensure the stability of omeprazole. This goal requires a multidisciplinary approach and continuous effort to design omeprazole formulations that meet quality standards and appropriate gastro-resistance requirements.

Five- versus seven-day dosing intervals of extended-release injectable omeprazole in the treatment of equine squamous and glandular gastric disease.

An extended-release injectable omeprazole formulation (ERIO) has become a popular treatment for equine squamous gastric disease (ESGD) and equine glandular gastric disease (EGGD) where it is available; however, published data are limited and optimal treatment regimens have not been determined. To compare effects of treatment on ESGD and EGGD when an ERIO formulation is administered at either 5- or 7-day intervals. Retrospective clinical study. Case records and gastroscopy images of horses with ESGD or EGGD treated with ERIO were reviewed. Images were anonymised and graded by one researcher masked to treatment group. Treatment responses were compared between the two treatment schedules using univariable ordered logistic regression. Forty-three horses were treated with ERIO at 5-day intervals and 39 horses at 7-day intervals. Signalment and presenting signs did not differ between groups. The proportions of horses with EGGD healing (to grade 0 or 1) in association with ERIO used at 5-day intervals (93%) were higher than associated with treatment at 7-day intervals (69%; odds ratio [OR]: 2.41, 95% CI: 1.23-4.74, p = 0.01). For ESGD, there was no significant difference in the proportion of horses healing in association with treatment at 5-day intervals (97%) compared with 7-day intervals (82%; OR: 2.75, 95% CI: 0.91-8.31, p = 0.07). Four of 328 injections were associated with an injection-site reaction (1%). Retrospective study design, lack of randomisation and limited case numbers. The use of ERIO at 5-day intervals might be more appropriate than the 7-day interval that is used currently.

A Comparison of the Efficacy of Two Omeprazole Formulations in the Treatment of Equine Gastric Ulcer Syndrome in Racehorses: A Blinded, Randomized Clinical Trial

Equine gastric ulcer syndrome (EGUS) is the most common disease of the stomach in horses and treatment is based on the oral administration of omeprazole for at least 28 days. Aim of this study was to compare the efficacy of two formulations of oral omeprazole—powder paste and gastro-enteric resistant granules—in the treatment of naturally occurring gastric ulcers in racehorses. Thirty-two adult racehorses, aged between 2 and 10 years old, with clinical signs of EGUS were included in this blinded, randomized clinical trial. Two gastroscopies were performed to evaluate gastric lesions in the squamous or glandular mucosa before and after 28 days of treatment. After the first gastroscopy, 2/32 horses were excluded because affected by equine squamous gastric disease (ESGD) 1/4. The remaining horses were divided into 4 groups, and were treated with 2 formulations of omeprazole (gastroenteric resistant granules, group 1, or powder paste, group 3) or with 2 placebo formulations (granules, group 2, or paste, group 4). Treatments were performed in the placebo horses affected by ESGD or equine glandular gastric disease after the T28 gastroscopy control. No differences were found between groups at T0. Differences were found between T0 vs. T28 for granular (P = .002) and powder paste (P = .01) formulations. No differences were detected between the two groups receiving omeprazole formulations at T28 (0.34) and between T0 vs. T28 for either of the groups receiving placebo treatments. For all the variables, the size of the effect was greater than 0.5, proving that the treatments had a considerable effect. Gastro-enteric resistant granules and powder paste omeprazole showed similar efficacy in the treatment of ESGD. The glandular mucosa responded poorly to treatment with omeprazole.

Pharmacokinetics and bioequivalence evaluation of omeprazole and sodium bicarbonate dry suspensions in healthy Chinese volunteers

Omeprazole and sodium bicarbonate dry suspension are effective treatments for acid-related disorders. This study compared the bioequivalence and safety of the two formulations of omeprazole and sodium bicarbonate powder and assessed how CYP2C19 gene polymorphisms affect pharmacokinetics (PK). A single-center, randomized, single-dose, 2-sequence and 2-period crossover method was performed in forty healthy Chinese subjects. Blood samples were collected after a single dose for PK (AUC0–∞, AUC0–t, and Cmax) analysis. The concentrations of Omeprazole in human plasma were determined by HPLC–MS/MS. Besides, the gene polymorphisms of CYP2C19 were assessed by Sanger sequencing. The geometric mean ratios (90% confidence interval) [GMR (95% CI)] of Test/Reference preparation for Cmax: 95.2% (88.48%, 102.43%), AUC0–t: 97.47% (94.4%, 101.02%), AUC0–∞: 97.68% (94.27%, 101.21%) were within the range of 80.00–125.00%. The non-parametric test showed no statistical difference in Tmax between the two groups (p > 0.05). All drugs were well tolerated, no severe adverse reactions occurred, and no significant differences in adverse events between the two drugs. For CYP2C19 gene polymorphisms, the results showed that of 40 subjects, 12 subjects were extensive metabolizers, 24 were intermediate metabolizers, and 4 were poor metabolizers, the frequency of metabolic genotypes were 30%, 60%, and 10%. And the allele distributions for CYP2C19 were *1, *2, and *3 at 60%, 38.75%, and 1.25%. Both the CYP2C19 alleles and metabolic genotypes were consistent with other studies in Chinese. The results of PK parameters showed that different genotypes of CYP2C19 lead to significant differences in t1/2, AUC0–t, AUC0–∞ and Cmax, but no significant differences in Tmax in each group. At the same time, we confirmed that the PK parameters of the test and reference had no differences between the males and females. This study has shown that the pharmacokinetic parameters of the two formulations are not significantly different, which showed bioequivalence and exemplary safety. CYP2C19 gene polymorphism significantly differed in the PK parameters of omeprazole sodium bicarbonate powder.

Evaluation of a long-acting injectable formulation of omeprazole in healthy dogs.

BackgroundTo evaluate the efficacy of a single intramuscular adminsitration of long‐acting omeprazole (LA‐OMEP) in increasing gastric pH in dogs.HypothesisWe hypothesized that LA‐OMEP would meet in healthy dogs the clinical goals defined for human patients for treatment of gastroduodenal ulceration.AnimalsNine healthy research dogs.MethodsProspective experimental study. Dogs were given a 4 mg/kg intramuscular injection of LA‐OMEP. Intragastric pH was continuously recorded on treatment days 0 to 7. Daily mean pH and mean percentage time (MPT) intragastric pH was ≥3 or ≥4 were determined.ResultsThe mean onset of action for the LA‐OMEP was 98.11 min (SD 46.39). The mean number of days the dogs' pH met established goals for MPT pH ≥3 was 5.5 days (range, 3‐7) and 5.25 days for MPT pH ≥4 (range, 3‐7). Long‐acting omeprazole met the human clinical goals pH ≥3 for 72 hours in 8/8 of the dogs and MPT pH ≥4 for 96 hours in 7/8 of dogs.Conclusions and Clinical ImportanceThe LA‐OMEP formulation produced gastric acid suppression in healthy dogs for an average of 5 days and up to 7 days, after a single intramuscular injection. No major adverse effects were observed.

Pharmacokinetic and Pharmacodynamic studies of Omeprazole Co-crystals dry suspension

A novel omeprazole co-crystals instant dry suspension dosage was formulated by applying co-crystallization which is a particle engineering technique to enhance the physicochemical properties. As omeprazole has major critical draw backs in their solubility and stability (acidic pH degradation, thermal sensitivity, photosensitivity and highly hygroscopic nature) bioavailability of omeprazole was drastically reduced and purpose of administration of drug was not fulfilled. There by this formulation was invented to check maid these problems. In this present study in-vivo evaluation were performed. Pharmacokinetic parameters and pharmacodynamic parameters were determined and statistically analysed. The prepared formulation of omeprazole produced reliable satisfaction in solving the drawback problems of pure omeprazole by enhancing bioavailability. Statistical analysis was done by one way ANOVA test with P value less than 0.0001, Dunnet multiple comparison test was performed between the groups with P value < 0.01 which was considered to be significant.

INHIBITION OF GASTRIC DEGRADATION OF OMEPRAZOLE USING A pH-SENSITIVE POLYMER AS A BINDER IN TABLET FORMULATION

Objective: This work was aimed at formulating omeprazole tablets using afzelia gum as a binder that is capable of inhibiting the gastric degradation of the drug. Methods: Afzelia gum at different concentrations of 0, 5, 10, 15, 20 and 30% was used as a binder to formulate omeprazole tablets. The tablets were formulated by direct compression and the batches labelled F1 to F6 respectively. A batch containing 15% hydroxypropyl methylcellulose (F7) was also formulated. The tablets were characterized; and dissolution in a pH 1.2 dissolution medium over 120 min period was studied. Aliquots taken every 20 min were analyzed by ultraviolet spectrophotometry to determine the amount of drug released and not degraded. Results: Amounts of drug released and not degraded at time 120 min were 53.1%, 57.3%, 57.8%, 58.8%, 62.1%, 83.4% and 90.0% for F1 to F7 respectively. Conclusion: Afzelia gum at a concentration of 30% is suitable for use as a binder in tablet formulation of omeprazole to ensure substantial inhibition of gastric degradation of the drug.

Clinical efficacy, safety and pharmacokinetics of a novel long‐acting intramuscular omeprazole in performance horses with gastric ulcers

SummaryOral omeprazole is used in the management of equine gastric ulcer syndrome (EGUS). However, its use may have limitations with regard to individual variation in absorption and the impact of dietary management on bioavailability. The objective of this study was to determine whether a novel compounded long‐acting injectable omeprazole (LAO‐USA) formulation would provide consistent serum omeprazole concentrations and to determine whether it was clinically safe and efficacious in the reduction of EGUS. Twenty‐three horses with EGUS described as having evidence of equine squamous gastric disease (ESGD) and/or equine glandular gastric disease (EGGD) received a 5 mg/kg bwt intramuscular injection of LAO‐USA once every 7 days for four doses. Gastroscopy was performed prior to the study and at Days 14 and 28. Pharmacokinetic analysis was performed to determine omeprazole concentrations over 7 days. Safety was measured by monitoring injection site reactions daily and bloodwork screening prior to and following the study. Of the horses with ESGD, 78% had improvement by Day 14 (p = 0.0035), with no further improvement from Day 14 to 28 (p > 0.99). ESGD grades from Day 0 to 28 decreased significantly (95% CI −1.92 to −0.91 grades) (p = 0.0002). Out of the horses (6/23) that had glandular lesions, 5/6 healed over time; however, this was not a significant change (p = 0.75). Injection reactions included oedema, heat and pain at the injection site. Considering the total number of injections across the whole study, 23% of horses experienced an injection site reaction. The number of injection site reactions increased following each dose (8%, 13%, 22% and 48%, respectively). The formulation did not appear to have adverse systemic effects. Serum omeprazole meanCmaxwas 46.2 ng/ml (±17.4 ng/ml), and these concentrations maintained at approximately 9.6 ng/ml (±4.6 ng/ml) for 7 days following dosing. This formulation is compounded and has not completed FDA investigation, which may increase formulation variability as it is produced or stored. The lack of control groups and potential bias in lesion grading are additional recognised limitations. The results of this study provide preliminary safety and efficacy data with regard to a novel LAO‐USA formulation. Future study is warranted to describe safety and efficacy for both ESGD and EGGD and would support further FDA investigation.

Factors Contributing to Drug Release From Enteric-Coated Omeprazole Capsules: An In Vitro and In Vivo Pharmacokinetic Study and IVIVC Evaluation in Beagle Dogs.

This study was performed to explore factors influencing the release of the proton pump inhibitor omeprazole from enteric-coated capsules in vitro and absorption in vivo in beagle dogs. Enteric-coated pellets with different enteric coating materials and coating levels were designed and prepared. All self-prepared formulations were characterized in vitro as well as in vivo and compared to the brand and generic commercial products. Evaluation of the corresponding release profiles suggested that coating material was the most critical factor. Enteric coating level determined the lag time before initiation of drug release, and subcoating level affected the drug release rate. Pharmacokinetic studies were performed in beagle dogs to further confirm the influence of formulation factors on drug absorption. Medium at pH 6.8 was a more biorelevant condition for in vitro drug release tests, although medium at pH 6.0 was better for discriminating release profiles of different formulations. A multiple level C in vitro/in vivo correlation was preliminarily established by which Tmax and Cmax of omeprazole formulations could be predicted with release parameters such as Tlag and T25. These results may facilitate quality evaluation and potentially improve the clinical efficacy of generic omeprazole products.

Re-evaluation of the regulation of omeprazole in racehorses: An evidence-based approach.

Medication control and doping control have been established in horse racing to ensure the integrity of the sport and the welfare of the horses. This ensures that horses do not compete under the influence of any drugs, including omeprazole, a therapeutic medication used to treat equine gastric ulcer syndrome. In this study, pharmacokinetic data were produced in equine plasma and urine following an oral administration of 4mg/kg of generic buffered formulation of omeprazole to six Thoroughbred horses in five daily doses to determine an appropriate screening limit and detection time in equine plasma and to assess whether the current detection time of 72hr in equine urine would be applicable when an alternative omeprazole product is administered. Cmax of 436-2,432ng/ml and AUC0-tau of 1,476-4,371nghrml-1 were obtained for plasma and indicated, in conjunction with other published oral omeprazole studies, that an appropriate plasma screening limit would be 500pg/ml with a detection time of 48hr. Urine analysis showed that omeprazole could be detected for up to 25hr above the previously established urine screening limit of 500pg/ml and thus indicated that the detection time advice could be potentially reduced from 72 to 48hr to allow more comprehensive treatment of gastric lesions.

Corrigendum.

Equine Veterinary JournalVolume 50, Issue 2 p. 278-278 CorrigendumFree Access Corrigendum This article corrects the following: Preliminary investigations into a novel, long-acting, injectable, intramuscular formulation of omeprazole in the horse B. W. Sykes, K. Kathawala, Y. Song, S. Garg, S. W. Page, C. Underwood, P. C. Mills, Volume 49Issue 6Equine Veterinary Journal pages: 795-801 First Published online: May 17, 2017 First published: 02 February 2018 https://doi.org/10.1111/evj.12792AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL The article 1 published in the November 2017 issue of Equine Veterinary Journal had an error in the first sentence of the Authors’ declaration of interest. The sentence read: B.W. Sykes is engaged as a consultant to Luoda Pharma Pty Ltd. It should have read: In addition to a part-time post as an Adjunct Associate Professor with The University of Queensland, B.W. Sykes is employed by Bova Australia, acts as an advisor to Bova UK and is a paid consultant to Luoda Pharma Pty Ltd. Reference 1Sykes, B.W., Kathawala, K., Song, Y., Garg, S., Page, S.W., Underwood, C. and Mills, P.C. (2017) Preliminary investigations into a novel, long-acting, injectable, intramuscular formulation of omeprazole in the horse. Equine Vet. J. 49, 795- 801. Volume50, Issue2March 2018Pages 278-278 ReferencesRelatedInformation

Quality of omeprazole purchased via the Internet and personally imported into Japan: comparison with products sampled in other Asian countries.

To evaluate the quality of omeprazole personally imported into Japan via the Internet and to compare the quality of these samples with previously collected samples from two other Asian countries. The samples were evaluated by observation, authenticity investigation and pharmacopoeial quality analysis. Quality comparison of some selected samples was carried out by dissolution profiling, Raman spectroscopy and principle component analysis (PCA). Observation of the Internet sites and samples revealed some discrepancies including the delivery of a wrong sample and the selling of omeprazole without a prescription, although it is a prescription medicine. Among the 28 samples analysed, all passed the identification test, 26 (93%) passed the quantity and content uniformity tests and all passed the dissolution test. Dissolution profiling confirmed that all the personally imported omeprazole samples remained intact in the acid medium. On the other hand, six samples from two of the same manufacturers, previously collected during surveys in Cambodia and Myanmar, frequently showed premature omeprazole release in acid. Raman spectroscopy and PCA showed significant variation between omeprazole formulations in personally imported samples and the samples from Cambodia and Myanmar. Our results indicate that the pharmaceutical quality of omeprazole purchased through the Internet was sufficient, as determined by pharmacopeial tests. However, omeprazole formulations distributed in different market segments by the same manufacturers were of diverse quality. Measures are needed to ensure consistent quality of products and to prevent entry of substandard products into the legitimate supply chain.

Enantiomeric Determination of Omeprazole and Esomeprazole by a Developed and Validated Chiral HPLC Method and Stability Studies by Microthermal Analysis

A rapid, accurate, precise, stability indicating and enantioselective chiral HPLC method was developed and validated for the quantitative (S)- and (R)- omeprazole in omeprazole formulations along with determination of enantiomeric purity of (S)- omeprazole in esomeprazole formulations according to the guidelines of the United States of Pharmacopeia (USP) and International Conference on Harmonization (ICH). The chromatographic separation was achieved with n-hexane/ 2-propanol/ acetic acid/ triethylamine (100 : 20 : 0.2 : 0.1, v/v) at a flow rate of 1.2 ml/min on Chiralcel OD-H and detected at 300 nm. The method showed good linearity, high sensitivity with detection limit (LOD) of 0.71 and 1.16 μg/ml and quantitation limit (LOQ) of 2.16 and 3.51 μg/ml for (S)- and (R)- omeprazole, respectively. The average percentage of recovery was found to be 100.85% to 101.36% for (S)- and 99.81% to 101.62% for (R)- omeprazole. The average percentage of relative standard deviation (% RSD) for intra- and inter- day precision were found to be 0.05% and 0.19% for (S)- and 0.03% and 0.13% for (R)- omeprazole, respectively. Stability study was performed under stress conditions. Microthermal analysis of omeprazole was also performed by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) to assess the physical and chemical behavior of the drug. The method was successfully applied to the quantitation of (S)- and (R)- omeprazole for omeprazole and as well as determination of (S)- omeprazole purity for esomeprazole formulations.Dhaka Univ. J. Pharm. Sci. 16(2): 221-233, 2017 (December)

A Comparative Dissolution Kinetics Test for Omeprazole-Containing Medicines, Reproducing Secretory and Motor-Evacuatory Impairments the Stomach of Patients with Acid-Dependent Diseases

A comparative dissolution kinetics test was used to study the release (dissolution kinetics) of an original and 10 generic formulations of omeprazole from different manufacturers in a medium simulating the moderately acidic conditions in the stomach typical of the state of medication-induced suppression of acidity; tests were also performed in a model of pathological duodenogastric reflux. HPLC was used to measure omeprazole concentrations in aliquots collected at 4, 10, 15, 20, 30, 45, and 60 min in solution with pH 7.0 ± 0.05 after 2 h of exposure at pH 1.2 ± 0.05 or 4.0 ± 0.05. The duration of action of pathological duodenogastric reflux on the therapeutic formulations of omeprazole was 4 min. Not all the study formulations could be completely recognized as equivalents to the original formulation in the in vitro test conditions.

Pharmacokinetic and pharmacodynamic effects of two omeprazole formulations on stomach pH and gastric ulcer scores.

Limited data are available on the relative pharmacokinetics and pharmacodynamics of different omeprazole formulations. To compare pharmacokinetic and pharmacodynamic effects of a novel omeprazole formulation against a currently registered product. Masked 2 period, 2 treatment crossover. Twelve clinically healthy horses were studied over two 6-day treatment periods. Horses were randomly assigned to receive a novel omeprazole paste (Ulcershield: ULS) or a currently registered reference omeprazole product (OMO). Gastric pH was measured continuously for 10 h on the day prior to commencing treatment (Day -1) and after 6 days of oral treatment (Day 5) using in situ antimony pH probes within an indwelling nasogastric tube. Plasma pharmacokinetics were determined on Days 0 and 6. Treatment significantly (P<0.005) increased gastric pH on Day 5, compared to results obtained prior to treatment (Day -1) and there was no significant difference between products (P = 0.773). Similarly, comparison of median hourly gastric pH (P = 0.593), mean gastric pH (P = 0.154), percentage time pH<4 (P = 0.259) and area under the time-gastric pH response curve (P = 0.734) did not discriminate between products. Both treatments resulted in significantly lower gastric ulcer severity scores (both P = 0.004), with no difference between treatments (P = 0.688). Comparison of mean log area under time-plasma concentration curves demonstrated that, although the lower limit of the 90% confidence interval was within the -20% limit for bioequivalence, the upper limit was exceeded, suggesting that the test product could have greater bioavailability than the reference product. The small sample size, large interhorse plasma omeprazole concentrations, and low bioavailability of omeprazole impacted the sensitivity of the bioequivalence analysis. ULS matched or slightly exceeded OMO plasma concentrations. Both products resulted in equivalent increases in gastric pH, gastric pH profiles and decrease in gastric ulcer scores. Thus, ULS was pharmacodynamically equivalent to OMO and was associated with an equivalent beneficial effect on gastric squamous mucosal ulceration.

Pharmacokinetics and tolerability of a new formulation of omeprazole in the horse.

A new formulation of omeprazole in gastro-resistant granules was tested with regard to its pharmacokinetics and tolerability. Twenty-four horses were randomly divided into three groups (8 horses/group) and treated, according a parallel study design, as follows: Group A untreated (control group), Group B received 4mg/kg of omeprazole, and Group C received 12mg/kg of omeprazole, both of which were treated orally once a day for 90days. Blood samples, taken from Group B subjects during the 1st and the 29th day of treatment at pre-established time points, were used to determine the concentration-time curves of omeprazole. The treatments were found to be safe and well tolerated by the horses. The serum hematological and biochemical values were within reference ranges for the entire observational time. No accumulation of the drug was found after 29days of treatment. Lower Cmax and AUCs were obtained at the 29th day of treatment.

Pharmacodynamics of a Long‐Acting Injectable Formulation of Omeprazole in the Horse

Pharmacodynamics of a Long‐Acting Injectable Formulation of Omeprazole in the Horse

Bioequivalence Study of Two Oral-Capsule Formulations of Omeprazole 20 mg in Combination with Sodium Bicarbonate in Healthy Mexican Adult Volunteers

In Mexico, the quick-release formulation of omeprazole 20 mg in mix with 1100 mg of sodium bicarbonate (oral capsules) is demonstrated for patients over 18 years for the treatment of gastritis, reflux, heartburn and the sensation of emptiness caused by the excessive acid creation.

Study of the effect of CYP2C19 polymorphisms on omeprazole pharmacokinetics by utilizing validated LC–MS/MS and Real Time-PCR methods

A fully automated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the determination of omeprazole in human plasma. Utilization of 96-well plates and robotic liquid handling workstations, rendered the whole procedure very fast, compared to the manual respective procedure of Liquid-Liquid Extraction (LLE). Sample analysis was performed by reversed phase LC-MS/MS, with positive electrospray ionization, using multiple reaction monitoring (MRM). The method required low plasma volumes and analysis of samples was completed in short run times. It was fully validated and applied to a pharmacokinetic study after per os administration of 20mg tablet formulations of omeprazole. The obtained concentrations were used for the calculation of the basic omeprazole pharmacokinetic parameters. Some variations observed in pharmacokinetic parameters among subjects were attributed to differences of CYP2C19 genotype. Therefore, a novel molecular method was developed in which DNA analysis was conducted by using Real Time-Polymerase Chain Reaction (Real Time-PCR). As source of biological material, Dried Blood Spots (DBS) were utilized, offering an alternative and advantageous strategy for such kind of studies.