Detection of Hypoglycemic Drugs in Human Urine Using Micellar Electrokinetic Chromatography

Nunez, Megan F.; Ferguson, Jayne E.; Machacek, Dwaine; Jacob, Gary S.; Oda, Robert P.; Lawson, George M.; Landers, James P.

doi:10.1021/ac00116a009

Cited by 46 publications

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“…Several methods have been reported for the extraction and detection of antidiabetic drugs in human plasma or urine: micellar electrokinetic capillary chromatography with diode-array detection 45 and high-performance liquid chromatography with ultraviolet detection. 46 However, most of them are timeconsuming, involving multiple extraction steps, and may provide false-positive results as a result of interferences with basal components of sample matrices or concomitant therapies.…”

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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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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“…Most methods are based on HPLC with ultraviolet (3 ), diode array (4 ), or fluorescence detection after derivatization of serum extracts (5 ). A micellar electrokinetic capillary chromatographic method with ultraviolet detection has also been proposed for the detection of sulfonylureas in urine (6 ). These methods may lack specificity, particularly when a single ultraviolet wavelength is used, which may cause false positives.…”

confidence: 99%

Identification and Quantification of 8 Sulfonylureas with Clinical Toxicology Interest by Liquid Chromatography–Ion-Trap Tandem Mass Spectrometry and Library Searching

et al. 2005

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Background: Identification of sulfonylureas in blood may be useful in the evaluation of hypoglycemic crises of unknown origin. The aim of the present study was to develop a highly selective liquid chromatography-electrospray tandem mass spectrometry (MS-MS) method using an ion-trap detector for rapid screening, identification, and quantification of sulfonylureas in human plasma. Methods: After standard liquid-liquid extraction with glisoxepide as an internal standard, 8 sulfonylureas (glibenclamide, glipizide, gliclazide, glibornuride, glimepiride, carbutamide, chlorpropamide, and tolbutamide) were eluted from a C 18 column within 10 min with an isocratic mobile phase. Drugs were identified and quantified in full-scan MS-MS mode by use of a homemade MS-MS library. We used the assay in 134 cases of hypoglycemic crises of unknown origin. Results: No ion suppression effect was noted for the analytes at their specific retention-time windows. For all drugs, assay validation showed good linearity (r

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“…Therapeutic use of the drug has resulted in the development of the many methods for its determination in body fluids and includes high performance liquid chromatography [2][3][4][5][6][7], gas-liquid chromatography [8][9][10][11], liquid chromatography-tandem mass spectrometry [12], micellar electrokinetic chromatography [13], electro spray mass spectrometry [14] and gas chromatography-mass spectrometry [15].…”

Section: Introductionmentioning

confidence: 99%

High Performance Liquid Chromatographic Assay of Chlorpropamide, Stability Study and its Application to Pharmaceuticals and Urine Analysis

Basavaiah¹

2017

Austin J Anal Pharm Chem

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Chlorproamide (CLP) is a sulphonyl-urea derivative used in the treatment of type 2 diabetes mellitus. A rapid, sensitive and specific HPLC method with uv detection is described for the determination of CLP in bulk and tablet forms. The assay was performed on an Inertsil ODS 3V (150mm × 4.6mm; 5µm particle size) column using a mixture of phosphate buffer (pH 4.5), methanol and acetonitrile (30:63:7v/v/v) as mobile phase at a flow rate of 1mLmin -1 and with uv detection at 254nm. The column temperature was 30ᴼC and injection volume was 20µL. The retention behaviour of CLP as a function of mobile phase pH, composition and flow rate was carefully studied, and chromatographic conditions, yielding a symmetric peak with highest number of theoretical plates, were optimized. The calibration curve was linear (r = 0.9999) over the concentration range 0.5 -300 µgmL -1 . The limits of detection (LOD) and quantification (LOQ) were found to be 0.1 and 0.3 µgmL -1 , respectively. Both intra-day and inter-day precisions determined at three concentration levels were below 1.0% and the respective accuracies expressed as %RE were ≤1.10%. Assays were performed under slightly altered chromatographic conditions, and the results were not significantly different from those obtained under optimum conditions, reflecting the robustness of the method. Inter-equipment and interanalysts deviations were insignificant testifying the ruggedness of the method. The method was validated for selectivity via placebo blank and synthetic mixture analyses. The method was applied to determine CLP in tablets and the results were comparable with those obtained by a reference method with respect to accuracy and precision. As part of stress testing, CLP was subjected to forced degradation under acid and base-induced hydrolysis, oxidation, heat and light, followed by assay using the developed method, and the results indicated that the drug was prone to oxidative degradation, but inert to other stress-conditions. The method was sensitive and selective enough to determine the drug content in spiked urine, and the results were satisfactory.Keywords: Chlorpropamide; Assay; HPLC; Pharmaceuticals; Stabilityindicating Pharmacopeia [16] which has adopted an HPLC-uv detection method for the assay of CLP. British Pharmacopeia [17] describes a spectrophotometric method whereas European Pharmacopeia [18] offers a titrimetric method for the assay in tablets and bulk drug, respectively. In addition to the above, CLP in pharmaceuticals has been assayed by several other techniques such as titrimetry [19], spectrophotometry [20][21][22][23], electrophoresis [24], thinlayerchromatoghraphy [25,26] and coulometry [27].HPLC, which finds immense applications in the analysis of body fluids for CLP [2][3][4][5][6][7], has also been applied to the determination of drug in pharmaceuticals, chiefly due to its sensitivity, selectivity, speed and wide applicability. El-Gizawy [28] has reported an HPLC method for the determination of CLP in tablets. The author used a Zorbax SAX ...

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Detection of Hypoglycemic Drugs in Human Urine Using Micellar Electrokinetic Chromatography

Cited by 46 publications

References 0 publications

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

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

Identification and Quantification of 8 Sulfonylureas with Clinical Toxicology Interest by Liquid Chromatography–Ion-Trap Tandem Mass Spectrometry and Library Searching

High Performance Liquid Chromatographic Assay of Chlorpropamide, Stability Study and its Application to Pharmaceuticals and Urine Analysis

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