Simultaneous high-performance liquid chromatographic analysis of omeprazole and its sulphone and sulphide metabolites in human plasma and urine

Mihaly, G W; Prichard, Peter J; Smallwood, Richard A.; Yeomans, Neville D; Louis, William J.

doi:10.1016/s0378-4347(00)84790-8

Cited by 40 publications

(16 citation statements)

References 5 publications

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“…The shorter run time allows for more samples to be analyzed per day. Due to poor stability of PPIs under acidic conditions, previous methods have performed chromatographic separation at pH of 7.0 or greater (3,6,8,9,26). Kobayashi et al have reported a simple method for OPZ and its metabolites determination with a more expensive alkalineresistant column (6).…”

Section: Discussionmentioning

confidence: 99%

Improved HPLC Method for Determination of Four PPIs, Omeprazole, Pantoprazole, Lansoprazole and Rabeprazole in Human Plasma

et al. 2010

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-PURP OSE:To develop a simple and rapid HPLC method for measuring of four proton-pump inhibitors (PPIs), omeprazole (OPZ), pantoprazole (PPZ), lansoprazole (LPZ) and rabeprazole (RPZ) concentrations in human plasma. METHODS: Following a single step liquid-liquid extraction analytes along with an internal standard (IS) were separated using an isocratic mobile phase of phosphate buffer (10 mM)/acetonitrile (53/47, v/v adjusted pH to 7.3 with triethylamine) at flow rate of 1 mL/min on reverse phase TRACER EXCEL 120 ODS-A column at room temperature. RESULTS: Total analytical run time for selected PPIs was 10 min. The assays exhibited good linearity (r 2 >0.99) over the studied range of 20 to 2500 ng/mL for OPZ, 20 to 4000 ng/mL for PPZ, 20 to 3000 ng/mL for LPZ and 20 to 1500 ng/mL for RPZ. The recovery of method was equal or greater than 80% and lower limit of quantification (LLOQ) was 20 ng/mL for four PPIs. Coefficient of variation and error at all of the intra-day and inter-day assessment were less than 9.2% for all compounds. CONCLUSIONS: The results indicated that this method is a simple, rapid, precise and accurate assay for determination of four PPIs concentrations in human plasma. This validated method is sensitive and reproducible enough to be used in pharmacokinetic studies and also is time-and cost-benefit when selected PPIs are desired to be analyzed.

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Section: Discussionmentioning

confidence: 99%

Improved HPLC Method for Determination of Four PPIs, Omeprazole, Pantoprazole, Lansoprazole and Rabeprazole in Human Plasma

et al. 2010

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“…Omeprazole concentrations were measured by high-performance liquid chromatography [11], Pharmacokinetic and Statistical Analysis. Attainment of steady-state plasma drug levels was evaluated by testing whether the gradient derived from the least-squares regres sion analysis of plasma concentration versus time data was significantly different from zero.…”

Section: Methodsmentioning

confidence: 99%

Placental Transfer of Omeprazole in Maternal and Fetal Sheep

Ms¹,

Dj²,

Gw³

et al. 1986

Dev Pharmacol Ther

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The placental transfer of omeprazole was studied over a 4-fold dose range in 7 nonanesthetized near-term pregnant sheep. There was a 5 to 1 maternal to fetal transplacental gradient of steady-state total omeprazole concentrations after both low dose (maternal plasma 556 ± 361 ng/ml, fetal plasma 101 ± 57 ng/ml) and high dose (maternal plasma 2,660 ± 1,130 ng/ml, fetal plasma 563 ± 182 ng/ml). Although this was in part due to differences in plasma protein binding between mother (unbound fraction 6.6 ± 5.5%) and fetus (unbound fraction 11.9 ± 2.4%), a 2 to 1 maternal to fetal gradient of steady-state unbound omeprazole concentration was still present (144 ± 73 ng/ml vs. 64 ± 32 ng/ml). Fetal omeprazole total plasma concentrations correlated strongly with maternal total drug concentrations (r = 0.84, p < 0.025) and with the inverse of maternal omeprazole total systemic clearance (r = 0.77, p < 0.05), indicating that maternal drug disposition was a major determinant of fetal omeprazole plasma concentrations. Urinary clearance of omeprazole was low in both mother (0.137 ± 0.046 ml/min) and fetus (0.067 ± 0.039 ml/min). This study demonstrates that the fetus is exposed to about one half of the unbound omeprazole concentration in maternal plasma and suggests that the extent of fetal exposure is largely dictated by maternal drug distribution and elimination characteristics. Introduction

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“…The omeprazole was measured by high performance liquid chromatography in the Gastroenterology Unit, Austin Hospital (Mihaly et al 1983). …”

Section: Omeprazole Assaymentioning

confidence: 99%

Nature of the Gastric Acid‐gastrin Feedback Loop in the Fetal Sheep

Shulkes

Chick

Hardy

1987

Clin Exp Pharma Physio

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1. The neonates of sheep and other species have a decreased gastric acid secretion but an elevated plasma gastrin concentration. 2. Since low gastric acid secretion is a stimulus for gastrin release in mature animals the present study examined whether the relative hypochlorhydria in the sheep fetus was sustaining the hypergastrinaemia. 3. Fetal plasma gastrin was measured following fetal gastric acidification (pentagastrin infusion) and gastric neutralization (parietal cell blockade with the proton pump inhibitor omeprazole) in chronically cannulated fetal sheep from 101 days until term (145 days). 4. Acutely raising gastric pH with omeprazole increased plasma gastrin in the mature sheep. However, in the fetus increasing the pH with omeprazole or decreasing pH with pentagastrin had no effect on fetal plasma gastrin. This was true for fetuses from all age groups. 5. The results indicate that the gastric acid-gastrin feedback loop is not functional in the fetus and that the hypergastrinaemia at birth is therefore not the result of the relative hypochlorhydria. 6. The time after birth when the gastric acid-gastrin feedback loop matures remains to be determined.

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Simultaneous high-performance liquid chromatographic analysis of omeprazole and its sulphone and sulphide metabolites in human plasma and urine

Cited by 40 publications

References 5 publications

Improved HPLC Method for Determination of Four PPIs, Omeprazole, Pantoprazole, Lansoprazole and Rabeprazole in Human Plasma

Improved HPLC Method for Determination of Four PPIs, Omeprazole, Pantoprazole, Lansoprazole and Rabeprazole in Human Plasma

Placental Transfer of Omeprazole in Maternal and Fetal Sheep

Nature of the Gastric Acid‐gastrin Feedback Loop in the Fetal Sheep

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