Development and validation of a rapid and sensitive assay for simultaneous quantification of midazolam, 1′-hydroxymidazolam, and 4-hydroxymidazolam by liquid chromatography coupled to tandem mass-spectrometry

High-throughput assay for simultaneous quantification of the plasma concentrations of morphine, fentanyl, midazolam and their major metabolites using automated SPE coupled to LC–MS/MS

“…For example, protein precipitation is a fast method that has been utilized previously for the quantification of fentanyl and its two metabolites [16], midazolam, 1-OH-MDZ and 4-OH-MDZ [20], as well as morphine and M3G in plasma samples [10]. However, this approach compromises the cleanliness of the samples, and it is not economical due to damage to the column and potential contamination of the detector.…”

“…Previously, separate LC-MS/MS assay methods for quantification of the plasma concentrations of morphine, M3G and M6G [9][10][11][12][13]; fentanyl and norfentanyl [14][15][16][17][18][19]; midazolam, 1-OH-MDZ and 4-OH-MDZ [20][21][22][23][24][25] have been described in the literature. Here, we have successfully extracted all eight of these analytes of interest from a single 150 L plasma sample using a single polymeric cartridge and on-line SPE with subsequent LC-MS/MS quantification.…”

Determination of midazolam and 1-hydroxymidazolam from plasma by gas chromatography coupled to methane negative chemical ionization mass spectrometry after sublingual administration of midazolam

“…In addition, a highly sensitive negative chemical ionization (NCI) in combination with GC-MS has been used [22,23]. Midazolam and its metabolites have been analysed without derivatization with liquid chromatography mass spectrometry (LC-MS) with positive mode electospray ionization (ESI) and a single quadrupole [24][25][26] or a triple quadrupole instrument [27][28][29][30]. In addition to chromatographic techniques micellar electrokinetic capillary chromatography (MECC) has been used for the confirmation of benzodiazepine compounds in human urine which tested positive by immunoassay screening [31].…”

“…Midazolam and its phase I metabolites have been analysed from plasma and liver microsomal incubations after simple protein precipitation with acetonitrile [30]. Dostalek et al [30] used a highly selective triple quadrupole mass spectrometer (MS/MS) for the analysis and reported the method to be selective and free from any matrix effect.…”

“…Midazolam and its phase I metabolites have been analysed from plasma and liver microsomal incubations after simple protein precipitation with acetonitrile [30]. Dostalek et al [30] used a highly selective triple quadrupole mass spectrometer (MS/MS) for the analysis and reported the method to be selective and free from any matrix effect. In ESI-LC/MS instruments in combination with the SIM mode, biological samples require an additional purification step to remove interfering components in order to obtain cleaner sample extracts and matrix effect free spray in the ion source [35,36].…”