RP‐HPLC method with electrochemical detection for the determination of metoclopramide in serum and its use in pharmacokinetic studies

Abstract

A rapid and sensitive reversed-phase high performance liquid chromatographic method has been developed for the determination of metoclopramide in serum. The assay was performed after single extraction with ethyl ether using methyl parahydroxybenzoate as internal standard. Chromatographic separations were performed on C(18) stationary phase with a mobile phase composed of methanol-phosphate buffer pH 3 (30:70 v/v). Analytes were detected electrochemically. The quantification limit for metoclopramide in serum was 2 ng mL(-1). Linearity of the method was confirmed in the range of 5-120 ng mL(-1) (correlation coefficient 0.9998). Within-day relative standard deviations (RSDs) ranged from 0.3 to 5.5% and between-day RSDs from 0.8 to 6.0%. The analytical method was successfully applied for the determination of pharmacokinetic parameters after ingestion of 10 mg dose of metoclopramide. Studies were performed on 18 healthy volunteers of both sexes.

Identification of Novel Metoclopramide Metabolites in Humans: In Vitro and In Vivo Studies

“…The pharmacokinetics of MCP have been characterized in humans and other mammalian species (Bakke and Segura, 1976;Bateman, 1983;McDermed et al, 1985;Lamparczyk et al, 2001;Kim et al, 2002;Vlase et al, 2006;Zaki et al, 2006). Significant interspecies differences have been reported in MCP metabolism (Bakke and Segura, 1976;Cowan et al, 1976;Bateman, 1983).…”

“…Because MCP metabolites were not available as synthetic standards, it was not possible to determine the extent of metabolite formation or to compare metabolites and determine quantitatively major metabolites. The average elimination halflife of MCP is approximately 5 h (Bateman, 1983;Lamparczyk et al, 2001;Vlase et al, 2006); therefore, full urine collection for 5 halflives (24 h) was conducted. In the urine samples, MCP levels were found to be 3.6-fold variable in the eight subjects.…”

Metoclopramide stimulates catecholamine- and granin-derived peptide secretion from pheochromocytoma cells through activation of serotonin type 4 (5-HT4) receptors

“…K7 M metoclopramide, which corresponds to the level of metoclopramide commonly observed in plasma after oral intake of 10 mg of the drug (Lamparczyk et al 2001), was sufficient to trigger a significant increase (i.e.,C20G4% for norepinephrine and C23G4% for epinephrine) in catecholamine secretion. Metoclopramide also induced a concentration-dependent increase in EM66 and WE14 productions (Fig.…”

Sensitive and selective liquid chromatography–tandem mass spectrometry method for the determination of metoclopramide in human plasma: application to a bioequivalence study

“…The reported bioanalytical methods for the quantifi cation of MCP in biological fl uids were based on either gas chromatography/mass spectrometry (Bateman et al, 1978;Jones et al, 1993;Riggs et al, 1994) or high-performance liquid chromatography with ultra violet detection (Graff ner et al, 1979;Popovic, 1984;Riley, 1984;de Jong et al, 1987;Albani et al, 1987;Takahashi et al, 1987;Fairhead et al, 1989;Buss et al, 1990;Lamparczyk et al, 2001), fl uorescence detection (Horiuchi et al, 2006;Vlase et al, 2006) and electrochemical detection (Zaki et al, 2006). The major disadvantages of all these methods include the use of a large amount of biological samples (0.5-2.0 mL plasma or urine samples), complicated extraction procedures or long chromatographic run time.…”