Identification of metoclopramide metabolites in the urine of cattle by gas chromatography-mass spectrometry and high-performance liquid chromatography-photodiode array detection

Abstract

The urinary metabolites of metoclopramide (4-amino-5-chloro-N-[2-diethylaminoethyl]-2-methoxybenzamide) were identified in cows. The drug was administered intravenously, voided urine was collected, and individual urine extracts were analysed by gas chromatography-mass spectrometry and high-performance liquid chromatography-photodiode array detection. The parent compound and one major metabolite (4-amino-5-chloro-N-[2-(ethylamino)ethyl]-2-methoxybenzamide) were common to all individuals. In addition to the parent and major metabolite, a second, minor metabolite was identified in two cows as 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-hydroxybenzamide. The identity of the minor metabolite was confirmed by comparison with a standard synthesized by a new method. Metabolite identification and characterization in food animal species allows the design of safety and environmental impact studies and relative metabolite ratios between dose treatment groups.

Simple and Sensitive Method for Measurement of Metoclopramide in Cattle Plasma by LC-MS/MS Using a Multimode Chromatography

“…have been reported in humans and goats after administration of McP [2, 7,8], as this agent readily crosses the blood-brain barrier [6]. Although there is a large amount a pharmacokinetic data available in humans [3,4,[12][13][14]16], there is little data about the McP concentration in serum and urine of cattle [9][10][11]. According to the pharmacokinetic study in Angus cows reported by Jones et al [11], McP was administered intravenously at a dose of 4 mg/kg.…”

“…Analytical methods for the determination of McP in blood samples include high performance liquid chromatography with a UV detector (HPLc-UV) [4,8,9,11,13,14], Gc-MS [3,10,15] and Lc-tandem mass spectroscopy (Lc-MS/MS) [12,16]. Of these methods, the Lc-MS/MS method has a highest detection sensitivity in human plasma, e.g., 0.78 ng/ ml (limit of quantitation: LOQ) according to Yan et al [16].…”

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.…”

Determination of metoclopramide in human plasma by LC–ESI-MS and its application to bioequivalance studies

“…The techniques adopted include gas chromatography-mass spectrometry (GC-MS) [2][3][4], electrogenerated chemiluminescence (ECL) [5] and high performance liquid chromatography (HPLC) methods with UV [6][7][8][9][10][11][12][13][14], fluorescence [15] or electrochemical detection [16]. The above methods have poor sensitivity and specificity for the determination of metoclopramide in plasma after administration of low dosages.…”