Detection of anti-diabetics in equine plasma and urine by liquid chromatography–tandem mass spectrometry

Ho, Emmie N.M.; Yiu, Kenneth C. H.; Wan, Terence S.M.; Stewart, Brian D.; Watkins, Kevin

doi:10.1016/s1570-0232(04)00641-5

Cited by 75 publications

(33 citation statements)

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“…For the extraction, different organic solvents and mixtures were also evaluated, including ethyl acetate, diethyl ether, and dichloromethane. The liquid-liquid extraction described in the literature [9] showed recoveries of repaglinide in human plasma of 78.0%, lower than that reported in this present work by 18%. Data representing the absolute analytical recovery are shown in Table 3.…”

Section: Sample Extraction and Recoverycontrasting

confidence: 81%

“…Several analytical methods for the quantitative determination of repaglinide in pure as well as pharmaceutical formulations were reported [2]- [6], but there are a limited number of analytical methods describing the determination of repaglinide in biological samples [7]- [9]. One method is based on electrochemical detection [7] and another is based on UV detection [8] after HPLC separations.…”

Section: Repaglinide (S)-2-ethoxy-4-[2-[[3-methyl-1-[2-(1-piperidinymentioning

confidence: 99%

“…An analytical method for the analysis of repaglinide in equine plasma using liquid chromatography coupled with tandem mass spectrometry has also been reported with a limit of detection of 1 ng/ml [9]. This method is more sensitive than the previously mentioned methods, but it was used only for screening purposes of 10 anti-diabetic drugs in horseracing without quantitative determination.…”

Section: Repaglinide (S)-2-ethoxy-4-[2-[[3-methyl-1-[2-(1-piperidinymentioning

confidence: 99%

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Liquid Chromatography Tandem Mass Spectrometry Method for Determination of Anti-Diabetic Drug Repaglinide in Human Plasma

Fayyad¹,

Ghanem²

2014

AJAC

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A highly sensitive, accurate and rapid analytical method based on reversed-phase liquid chromatography/electrospray ionization tandem mass spectrometry (RP-LC-ESI-MS/MS) has been developed and validated for the determination of repaglinide in human plasma using cetirizine as an internal standard (IS). The method was validated over a linear range of 0.5 -100 ng/ml. After addition of IS, analytes were extracted from the plasma samples by liquid-liquid extraction using tert-butyl methyl ether as. The dried residue was reconstituted with 500 μL of mobile phase consisting of water/methanol/acetonitrile (62.5:20:17.5, v/v/v) and 0.2% formic acid. Chromatographic separations were achieved on a C18 analytical column. The analytes were detected with a triple quadrupole mass spectrometer using turbo V ® ion spray source with positive ionization in multiple reaction monitoring (MRM) mode using MRM transitions m/z 453.3 > 162.2 and m/z 389.0 > 201.1 for the drug and IS, respectively. The proposed method was fully validated in terms of linearity, accuracy, precision, specificity, sensitivity, recovery and stability, giving results within the acceptable range. This method was successfully applied for a large number of authentic human plasma samples from a bioequivalence study.

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Section: Sample Extraction and Recoverycontrasting

confidence: 81%

Section: Repaglinide (S)-2-ethoxy-4-[2-[[3-methyl-1-[2-(1-piperidinymentioning

confidence: 99%

Section: Repaglinide (S)-2-ethoxy-4-[2-[[3-methyl-1-[2-(1-piperidinymentioning

confidence: 99%

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Liquid Chromatography Tandem Mass Spectrometry Method for Determination of Anti-Diabetic Drug Repaglinide in Human Plasma

Fayyad¹,

Ghanem²

2014

AJAC

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“…Very recently, an LC-MS method for the determination of antidiabetic drugs in equine plasma and urine was published. 48 So far, none of these laboratory methods has been used currently in medical practice. The LC-MS method could be an interesting method for the detection of antidiabetic drugs in human serum and/or urine in the future.…”

Section: Discussionmentioning

confidence: 99%

Factitious Hyperinsulinism Leading to Pancreatectomy: Severe Forms of Munchausen Syndrome by Proxy

Giurgea¹,

Ulinski

Touati³

et al. 2005

Pediatrics

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ABSTRACT. Clinical history and inappropriate insulin secretion during hypoglycemic episodes permit the diagnosis of hyperinsulinism. We report 2 cases of factitious hyperinsulinism leading to partial pancreatectomy. Case 1 was an 8-year-old girl who presented with severe hypoglycemia and elevated insulin and C-peptide levels. Catheterization of pancreatic veins was performed to localize the excess insulin secretion. Insulinoma was suspected, and partial pancreatectomy was performed. Ten days after surgery, severe hypoglycemia recurred with severely elevated plasma insulin levels (؋100) but very low C-peptide plasma levels, suggesting factitious hyperinsulinemia. Hypoglycemic episodes before surgery were provoked by oral sulfonamides; postoperative episodes were caused by parenteral insulin. Falsified prescriptions for sulfonamides and insulin by the mother, a nurse, were found. Case 2 was a 6-month-old girl who presented with seizures and hypoglycemia but had a symptom-free interval of many months afterward. At 2 years of age, repeated hypoglycemic seizures and elevated insulin plasma levels suggested congenital hyperinsulinism. C-peptide plasma level, measured once, was normal, but blood sampling was performed 15 minutes after a hypoglycemic episode. Partial pancreatectomy was performed. Two weeks after surgery, hypoglycemic seizures recurred, and the patient was admitted for pancreatic vein catheterization. This investigation was performed during hypoglycemia and revealed high insulin levels and undetectable C-peptide levels, suggesting factitious hypoglycemia. Insulin/C-peptide ratio analysis is crucial to assess factitious hypoglycemia, although sulfonamide-induced hypoglycemia is not thereby detected. P ersistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a profound hypoglycemia resulting from excess insulin secretion. The diagnosis of PHHI is based on the combination of the clinical history and the laboratory findings. The clinical presentation of PHHI varies with the age at onset of hypoglycemia. The neonatal form (ϳ60% of all patients) is characterized by hypoglycemia within 72 hours after birth, with ϳ50% of the patients exhibiting seizures. Irreversible brain damage may occur. Infantile-onset PHHI (35% of patients) occurs between the 1st and the 12th months of life, and, again, seizures occur in 50% of the patients. Approximately 5% of pediatric patients with PHHI present after 1 year of age. Laboratory findings of PHHI include fasting and postprandial hypoglycemia (Ͻ3 mmol/L) with hyperinsulinemia (plasma insulin concentrations Ͼ3 mU/L) and elevated C-peptide levels, requiring high rates of intravenous glucose (Ͼ10 mg/kg/min) to maintain blood glucose Ͼ3 mmol/L. Plasma glucose concentration increases by 2 to 3 mmol/L in response to 0.5 mg of glucagon injection. In the absence of clearly abnormal insulin levels during hypoglycemia, a 4-to 6-hour fasting study may reveal inappropriately low plasma levels of ketone bodies, free fatty acids, and branched-chain amino acids.The causes of PHHI includ...

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“…Repaglinide and its metabolites M1 and M4 were determined using liquid chromatography-tandem mass spectrometry according to methods published previously (Ho et al, 2004;Kajosaari et al, 2005b). Repaglinide was measured in plasma and urine, whereas both metabolites were determined in urine only because of their undetectable concentrations in plasma.…”

Section: Methodsmentioning

confidence: 99%

Effect of theCYP2C8Genotype on the Pharmacokinetics and Pharmacodynamics of Repaglinide

et al. 2011

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ABSTRACT:The pharmacokinetics of repaglinide shows pronounced interindividual variability, for which several reasons have been considered, including interactions with drugs inhibiting CYP2C8 and CYP2C8 genetic polymorphism. However, existing data on the role of genetic polymorphisms in repaglinide disposition are not fully consistent. We studied the effect of CYP2C8*3 on the pharmacokinetics and pharmacodynamics of repaglinide in 29 healthy whites carrying CYP2C8*3/*3 (n ‫؍‬ 4), CYP2C8*1/*3 (n ‫؍‬ 13), or CYP2C8*1/*1 (n ‫؍‬ 12). After administration of a single dose of 2 mg of repaglinide, blood was drawn for assessment of repaglinide pharmacokinetics and pharmacodynamics, and urine was collected to quantify the main repaglinide metabolites M1 and M4 up to 24 h postdose. Repaglinide and the metabolites were quantified by liquid chromatography-tandem mass spectrometry. Considering only the effect of CYP2C8*3, the mean (95% confidence interval) area under the time-concentration curve . In addition, for urinary metabolite excretion and pharmacodynamic parameters, i.e., mean and maximal changes in insulin and glucose concentration, no significant differences between CYP2C8 genotypes were observed. Likewise, no significant effects on the pharmacokinetics or pharmacodynamics were observed when AUC and C max of repaglinide were corrected for reported effects of the SLCO1B1 521T>C polymorphism or when both polymorphisms were tested in a two-way ANOVA. In conclusion, CYP2C8*3 does not seem to play an important role in the pharmacokinetics and pharmacodynamics of repaglinide given in a therapeutic dose.

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Detection of anti-diabetics in equine plasma and urine by liquid chromatography–tandem mass spectrometry

Abstract: An LC-MS-MS method has been developed for the simultaneous detection of 10 anti-diabetics in equine plasma and urine. This method can be used to detect the abuse of anti-diabetic drugs in racehorses.

Cited by 75 publications

References 0 publications

Liquid Chromatography Tandem Mass Spectrometry Method for Determination of Anti-Diabetic Drug Repaglinide in Human Plasma

Liquid Chromatography Tandem Mass Spectrometry Method for Determination of Anti-Diabetic Drug Repaglinide in Human Plasma

Factitious Hyperinsulinism Leading to Pancreatectomy: Severe Forms of Munchausen Syndrome by Proxy

Effect of theCYP2C8Genotype on the Pharmacokinetics and Pharmacodynamics of Repaglinide

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