Mixed‐mode SPE for a multi‐residue analysis of benzodiazepines in whole blood using rapid GC with negative‐ion chemical ionization MS

Abstract

A sensitive and selective method for simultaneous quantitation of 15 benzodiazepines in human whole blood using rapid GC with negative-ion chemical ionization MS is proposed. A mixed-mode cation-exchange polymeric sorbent was used for SPE. Different extraction solvents or mixtures of solvents of different compositions for elution of the adsorbed analytes, and washing steps for eliminating interferences in the column were tested. Analytes were eluted from the column using 5% v/v NH4 OH in methanol. A derivatization step using different silylation reagents, time, and temperature was tested. Extracts from SPE were silylated by a mixture of N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide, acetonitrile, ethyl acetate, and subjected to gas chromatographic analysis. The LODs of 15 benzodiazepines in whole blood samples ranged from 0.24-0.62 ng mL(-1). The RSDs of samples used for three different quality control concentration levels were lower than 7.0%, and the accuracy ranged from 89.5 to 110.5%. The results show that the developed method is accurate, sensitive, selective, and very fast. Finally, the applicability of this method for determination of trace concentrations of several benzodiazepines in real blood samples has been demonstrated.

Spectrofluorometric determination of clonazepam in dosage forms: Application to content uniformity testing and human plasma

“…Various methods were reported for estimation of CNP; including spectrophotometric methods, spectrofluorometric method based on reduction of nitro group to the corresponding amino group and then reacting the reduced form with 2‐cyanoacetamide in the presence of ammonia (25%), HPTLC, HPLC, LC/MS and GC . Most of these analytical methods are tedious and time consuming .…”

“…Most of these analytical methods are tedious and time consuming . Others require expensive and complex equipment, while others need labour‐intensive sample preparation …”

Development of an SPE method for the determination of zaleplon and zopiclone in hemolyzed blood using fast GC with negative-ion chemical ionization MS

“…The SPE column Oasis MCX was used in our experiment. This sorbent is characterized by good retention of polar and aromatic compounds due to hydrophilic–lipophilic interactions, and strong cation exchange groups for basic compounds due to ion‐exchange interactions .…”

“…The validation of the new method was done following the recommendation . The LOD and LOQ were determined as published previously . In order to evaluate the intraday variation, six replicates of four QC samples of different concentrations were extracted and analyzed within one day.…”

Microextraction by packed sorbent (MEPS)-UHPLC-UV: A simple and efficient method for the determination of five benzodiazepines in an alcoholic beverage

“…Numerous methods can be found in literature for the determination of BDZ for forensic and clinical purposes. Gas chromatography (GC) has been widely used as well, in combination with mass spectrometry (MS) or with other detectors such as nitrogen-phosphorous (NPD) and micro-electron capture (ECD) [1 and references therein-2] Hyphenated GC techniques are very sensitive and specific, yet some BDZ are thermolabile and require derivatization prior to analysis [3,4]. Other approaches include micellar electrokinetic chromatography using a cyanine dye for indirect laser-induced fluorescence detection and capillary zone electrophoresis (CZE) [5].…”