Analysis of benzodiazepines and their metabolites using DBS cards and LC–MS/MS

Lee, Heesang; Park, Yujin; Jo, Jiyeong; In, Sangwhan; Park, Yonghoon; Kim, Eun‐Mi; Pyo, Jae Sung; Choe, Sanggil

doi:10.1016/j.forsciint.2015.07.004

Cited by 26 publications

(20 citation statements)

References 24 publications

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“…Benzodiazepines' pharmacological effect is mainly based on the enhancement of the permeability of the chloride ions due to their interaction with the GABA A receptor located in the CNS. Hence, they are frequently used for the treatment of several disorders, such as insomnia, anxiety, seizures, convulsions, agitation, muscle spasms, and alcohol withdrawal . Identification of benzodiazepines in biological samples of forensic interest is common, and hundreds of studies on the toxic effects of this class of substances have been published to date.…”

Section: Introductionmentioning

confidence: 99%

“…for the treatment of several disorders, such as insomnia, anxiety, seizures, convulsions, agitation, muscle spasms, and alcohol withdrawal. 2 Identification of benzodiazepines in biological samples of forensic interest is common, and hundreds of studies on the toxic effects of this class of substances have been published to date. In particular, despite the high therapeutic index, 3,4 benzodiazepines are frequently directly and indirectly involved in the cause of death.…”

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confidence: 99%

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Determination of benzodiazepines in blood and in dried blood spots collected from post‐mortem samples and evaluation of the stability over a three‐month period

Moretti

Freni

Tomaciello

et al. 2019

Drug Testing and Analysis

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The aims of this study were (a) to develop a liquid chromatography−tandem mass spectrometry (LC–MS/MS) method for the identification of 27 benzodiazepines and metabolites in dried blood spots (DBSs) and in whole blood; (b) to compare the diagnostic reliability of DBSs with blood analyses; and c) to monitor analytes stability on DBSs within a three‐month period. Aliquots of 85 μL of blood from post‐mortem cases were pipetted on cards for DBS analysis. We also collected a tube of blood and stored it at − 20°C. The cards were allowed to dry at room temperature. For each case, DBSs were analyzed immediately (T0), within the following 3 weeks (T1, T2, T3) and after 3 months (T4). The method was applied to 60 post‐mortem cases. A screening procedure was applied to all 27 molecules, while the method was fully validated for the 9 molecules detected in real samples. Limits of detection (LODs) and limits of quantification (LOQs) were in the range 0.1–50.0 ng/mL and 5.0–100.0 ng/mL, respectively. Nine analytes were detected and quantitated in 14 cases: diazepam (n = 6, 58–162 ng/mL), desmethyldiazepam (n = 6, 99‐ > 500 ng/mL), 7‐aminoclonazepam (n = 5, 43‐ > 500 ng/mL), alprazolam (n = 2, 15 and 69 ng/mL), chlordesmethyldiazepam (n = 1, 55 ng/mL), desalkylflurazepam (n = 1, 270 ng/mL), flurazepam (n = 1, 50 ng/mL), medazepam (n = 1, 155 ng/mL), and midazolam (n = 1, 227 ng/mL). The concentrations on DBSs were in good agreement with those obtained on conventional blood samples (<20% variation). Except for midazolam (degraded in 1 week), desalkylflurazepam and medazepam (decreased more than 50% after three months), a good stability for a three‐month period was observed for most of the compounds detected in real post‐mortem samples.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Determination of benzodiazepines in blood and in dried blood spots collected from post‐mortem samples and evaluation of the stability over a three‐month period

Moretti

Freni

Tomaciello

et al. 2019

Drug Testing and Analysis

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“…Many analytical methods have been recently developed for determination of BDZs, in particular, high performance liquid chromatography (HPLC) coupled with diode array detector (DAD) [5,6] and tandem mass spectrometry (MS/MS) [7,8], gas chromatography (GC) in combination with MS [9], electrophoresis [10] and spectrofluorimetry [11]. These remarkable analytical methods are high sensitive and selective requiring low sample consumption and enabling simultaneous determination of plenty of miscellaneous analytes.…”

Section: Introductionmentioning

confidence: 99%

“…2 according to the supporting electrolyte used (BR buffers of pH[5][6][7][8][9][10][11]. The excellent analytical performance for BDZs sensing mostly arises from high hydrogen overpotential and self-renewing atomically smooth surface of this electrode material.…”

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confidence: 99%

Mercury-free and modification-free electroanalytical approach towards bromazepam and alprazolam sensing: A facile and efficient assay for their quantification in pharmaceuticals using boron-doped diamond electrodes

Samiec

Švorc

Stanković

et al. 2017

Sensors and Actuators B: Chemical

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“…Intra-assay coefficients of variation (CV) were calculated. DBS values were compared to WB results using linear regression, Bland-Altman plots and cross-validation models 7 . When capDBS values were applied to equations derived from regression analyses, results approached those of WB values.…”

Section: Population Disease Control and Clinicalmentioning

confidence: 99%

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2018

IJPSR

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Bioanalysis is a sub-discipline of analytical chemistry covering the quantitative measurement of xenobiotics (drugs and their metabolites and biological molecules in unnatural locations or concentration) and biotics (macromolecules, proteins, DNA, large molecule drugs, metabolites) in biological system. The focus of bioanalysis in the pharmaceutical industry is to provide as quantitative measure of the active drug and/or its metabolite(s) for the purpose of pharmacokinetics, toxicokinetics, bioequivalence and exposure response (pharmacokinetics / pharmacodynamics studies). Over the past several years dried matrix spot (DMS) sampling technique has emerged as a pertinent method in both qualitative and quantitative bioanalysis context. There are many types of DMS techniques such as dried blood spot (DBS), dried plasma spot (DPS), dried urine spot (DUS) and dried breast milk spot (DBMS). The most commonly used technique is DBS wherein the blood sample is directly soaked on to a paper (with or without treatment) and after drying it can be analyzed by modern analytical, immunological or genomic detection systems. Several advantages of DMS techniques such as low sample requirement, transportation and storage without special treatment, better analytes stability, enhanced clinical cooperation in clinical trials and reduced unforeseeable exposure of biohazard to analysts, make it the most appropriate sampling technique for bioanalysis. This review illustrates the available information on DBS, DPS, DUS and DBMS methods which may serve for investigators in the field of bioanalysis. Further, the proficiency and appliance of DMS method in pharmacokinetic (PK), therapeutic drug monitoring (TDM), toxicokinetic (TK), metabolomic and disease diagnosis is explored.

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Analysis of benzodiazepines and their metabolites using DBS cards and LC–MS/MS

Cited by 26 publications

References 24 publications

Determination of benzodiazepines in blood and in dried blood spots collected from post‐mortem samples and evaluation of the stability over a three‐month period

Determination of benzodiazepines in blood and in dried blood spots collected from post‐mortem samples and evaluation of the stability over a three‐month period

Mercury-free and modification-free electroanalytical approach towards bromazepam and alprazolam sensing: A facile and efficient assay for their quantification in pharmaceuticals using boron-doped diamond electrodes

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