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

Abstract

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

Solving signal instability to maintain the second-order advantage in the resolution and determination of multi-analytes in complex systems by modeling liquid chromatography–mass spectrometry data using alternating trilinear decomposition method assisted with piecewise direct standardization

“…As illustrated in Fig. 3, on one hand, six selected SOADs are eluted completely within 5.5 min, which is shorter than that of the traditional HPLC-UV method [69] and almost equal to that of MRM method [60][61][62]. However, it is not difficult to find that the chromatographic peaks of these compounds still overlap with each other seriously (see R S in Table S6) although this calibration sample only contains six target analytes without potential interferences.…”

“…However, most oral antidiabetics can cause life-threatening hypoglycaemias and can therefore be misused with suicidal or homicidal intent [60][61][62]. Besides, SOADs can be also used as a stopper in racehorses by reducing the blood glucose level [63].…”

“…The calibration set consisted of eleven samples in which eleven concentration levels of six analytes of interest were designed by an U 11 (11 6 ) uniform design [64]. According to the previously reported literature [60][61][62], the corresponding concentrations of six studied SOADs in eleven calibration samples (C01-C11) were designed as summarized in Table 1. In addition, a set of prediction samples consisting of five spiked human plasma samples (P01-P05) were designed and the concentrations of analytes were within the linear ranges of calibration samples.…”

A systematic and critical review on bioanalytical method validation using the example of simultaneous quantitation of antidiabetic agents in blood

“…None of the main guidelines describes how to evaluate LOD, nor do they require the assessment of this parameter. Despite this, 19 articles determined the LOD, considering it to be three times the blank plasma signal [7,[9][10][11]13,[16][17][18][19][24][25][26]29,31,32,35,[38][39][40], as suggested in the ICH guideline (for analytical method validation) [73]. Although not mandatory, the determination of LOD is interesting and must be considered when the qualitative identification of the drug is important information.…”

Comparative Study of Electrospray and Atmospheric Pressure Chemical Ionization with Liquid Chromatography–Mass Spectrometry for Quantification of Five Antihyperglycemic Agents Utilizing Monolithic Column

“…Ho et al (2004) reported LC-MS=MS method for simultaneous determination of 10 antidiabetic drugs comprising mainly sulfonylureas and thiazolidinediones in equine plasma and urine samples with an LOQ range of 1.0-10.0 ng=mL. Hoizey et al (2005) described simultaneous determination of eight sulfonylurea as based on LC-MS=MS with LOQ in the range of 7.8-78 ng=mL. Wang and Miksa (2007) have reported LC-ESI-MS=MS method for 10 antidiabetic drugs in plasma samples in SRM mode with LOQ in a range of 1.0-5.0 ng=mL.…”