Rapid determination of designer benzodiazepines, benzodiazepines, and Z-hypnotics in whole blood using parallel artificial liquid membrane extraction and UHPLC-MS/MS

Linda Vårdal; Gladys Wong; Åse Marit Leere Øiestad; Stig Pedersen-Bjergaard; Astrid Gjelstad; Elisabeth Leere Øiestad

doi:10.1007/s00216-018-1147-y

Rapid determination of designer benzodiazepines, benzodiazepines, and Z-hypnotics in whole blood using parallel artificial liquid membrane extraction and UHPLC-MS/MS

Linda Vårdal, Gladys Wong, Åse Marit Leere Øiestad, Stig Pedersen-Bjergaard, Astrid Gjelstad, Elisabeth Leere Øiestad^*

^*Corresponding author for this work

10 Citations (Scopus)

Abstract

Benzodiazepines (BZD) and Z-hypnotics are frequently analyzed in forensic laboratories, and in 2012, the designer benzodiazepines (DBZD) emerged on the illegal drug scene. DBZD represent a particular challenge demanding new analytical methods. In this work, parallel artificial liquid membrane extraction (PALME) is used for sample preparation of DBZD, BZD, and Z-hypnotics in whole blood prior to UHPLC-MS/MS analysis. PALME of BZD, DBZD, and Z-hypnotics was performed from whole blood samples, and the analytes were extracted across a supported liquid membrane (SLM) and into an acceptor solution of dimethyl sulfoxide and 200 mM formic acid (75:25, v/v). The method was validated according to EMA guidelines. The method was linear throughout the calibration range (R² > 0.99). Intra- and inter-day accuracy and precision, as well as matrix effects, were within the guideline limit of ± 15%. LOD and LLOQ ranged from 0.10 to 5.0 ng mL⁻¹ and 3.2 to 160 ng mL⁻¹, respectively. Extraction recoveries were reproducible and above 52%. The method was specific, and the analytes were stable in the PALME extracts for 4 and 10 days at 10 and − 20 °C. No carry-over was observed within the calibration range. PALME and UHPLC-MS/MS for the determination of DBZD, BZD, and Z-hypnotics in whole blood are a green and low-cost alternative that provides high sample throughput (96-well format), extensive sample clean-up, good sensitivity, and high reproducibility. The presented method is also the first method incorporating analysis of DBZD, BZD, and Z-hypnotics in whole blood in one efficient analysis. [Figure not available: see fulltext.].

Original language	English
Journal	Analytical and Bioanalytical Chemistry
Volume	410
Issue number	20
Pages (from-to)	4967-4978
Number of pages	12
ISSN	1618-2642
DOIs	https://doi.org/10.1007/s00216-018-1147-y
Publication status	Published - 2018

Keywords

Benzodiazepines
Designer benzodiazepines
LC-MS/MS
Parallel artificial liquid membrane extraction
Whole blood samples
Z-hypnotics
Limit of Detection
Tandem Mass Spectrometry/economics
Humans
Benzodiazepines/analysis
Membranes, Artificial
Equipment Design
Designer Drugs/analysis
Hypnotics and Sedatives/analysis
Liquid-Liquid Extraction/economics
Time Factors
Chromatography, High Pressure Liquid/economics

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10.1007/s00216-018-1147-y

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Vårdal, L., Wong, G., Øiestad, Å. M. L., Pedersen-Bjergaard, S., Gjelstad, A., & Øiestad, E. L. (2018). Rapid determination of designer benzodiazepines, benzodiazepines, and Z-hypnotics in whole blood using parallel artificial liquid membrane extraction and UHPLC-MS/MS. Analytical and Bioanalytical Chemistry, 410(20), 4967-4978. https://doi.org/10.1007/s00216-018-1147-y

Rapid determination of designer benzodiazepines, benzodiazepines, and Z-hypnotics in whole blood using parallel artificial liquid membrane extraction and UHPLC-MS/MS. / Vårdal, Linda; Wong, Gladys; Øiestad, Åse Marit Leere et al.
In: Analytical and Bioanalytical Chemistry, Vol. 410, No. 20, 2018, p. 4967-4978.

Research output: Contribution to journal › Journal article › Research › peer-review

Vårdal, L, Wong, G, Øiestad, ÅML, Pedersen-Bjergaard, S, Gjelstad, A & Øiestad, EL 2018, 'Rapid determination of designer benzodiazepines, benzodiazepines, and Z-hypnotics in whole blood using parallel artificial liquid membrane extraction and UHPLC-MS/MS', Analytical and Bioanalytical Chemistry, vol. 410, no. 20, pp. 4967-4978. https://doi.org/10.1007/s00216-018-1147-y

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title = "Rapid determination of designer benzodiazepines, benzodiazepines, and Z-hypnotics in whole blood using parallel artificial liquid membrane extraction and UHPLC-MS/MS",

abstract = "Benzodiazepines (BZD) and Z-hypnotics are frequently analyzed in forensic laboratories, and in 2012, the designer benzodiazepines (DBZD) emerged on the illegal drug scene. DBZD represent a particular challenge demanding new analytical methods. In this work, parallel artificial liquid membrane extraction (PALME) is used for sample preparation of DBZD, BZD, and Z-hypnotics in whole blood prior to UHPLC-MS/MS analysis. PALME of BZD, DBZD, and Z-hypnotics was performed from whole blood samples, and the analytes were extracted across a supported liquid membrane (SLM) and into an acceptor solution of dimethyl sulfoxide and 200 mM formic acid (75:25, v/v). The method was validated according to EMA guidelines. The method was linear throughout the calibration range (R2 > 0.99). Intra- and inter-day accuracy and precision, as well as matrix effects, were within the guideline limit of ± 15%. LOD and LLOQ ranged from 0.10 to 5.0 ng mL−1 and 3.2 to 160 ng mL−1, respectively. Extraction recoveries were reproducible and above 52%. The method was specific, and the analytes were stable in the PALME extracts for 4 and 10 days at 10 and − 20 °C. No carry-over was observed within the calibration range. PALME and UHPLC-MS/MS for the determination of DBZD, BZD, and Z-hypnotics in whole blood are a green and low-cost alternative that provides high sample throughput (96-well format), extensive sample clean-up, good sensitivity, and high reproducibility. The presented method is also the first method incorporating analysis of DBZD, BZD, and Z-hypnotics in whole blood in one efficient analysis. [Figure not available: see fulltext.].",

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T1 - Rapid determination of designer benzodiazepines, benzodiazepines, and Z-hypnotics in whole blood using parallel artificial liquid membrane extraction and UHPLC-MS/MS

AU - Vårdal, Linda

AU - Wong, Gladys

AU - Øiestad, Åse Marit Leere

AU - Pedersen-Bjergaard, Stig

AU - Gjelstad, Astrid

AU - Øiestad, Elisabeth Leere

PY - 2018

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N2 - Benzodiazepines (BZD) and Z-hypnotics are frequently analyzed in forensic laboratories, and in 2012, the designer benzodiazepines (DBZD) emerged on the illegal drug scene. DBZD represent a particular challenge demanding new analytical methods. In this work, parallel artificial liquid membrane extraction (PALME) is used for sample preparation of DBZD, BZD, and Z-hypnotics in whole blood prior to UHPLC-MS/MS analysis. PALME of BZD, DBZD, and Z-hypnotics was performed from whole blood samples, and the analytes were extracted across a supported liquid membrane (SLM) and into an acceptor solution of dimethyl sulfoxide and 200 mM formic acid (75:25, v/v). The method was validated according to EMA guidelines. The method was linear throughout the calibration range (R2 > 0.99). Intra- and inter-day accuracy and precision, as well as matrix effects, were within the guideline limit of ± 15%. LOD and LLOQ ranged from 0.10 to 5.0 ng mL−1 and 3.2 to 160 ng mL−1, respectively. Extraction recoveries were reproducible and above 52%. The method was specific, and the analytes were stable in the PALME extracts for 4 and 10 days at 10 and − 20 °C. No carry-over was observed within the calibration range. PALME and UHPLC-MS/MS for the determination of DBZD, BZD, and Z-hypnotics in whole blood are a green and low-cost alternative that provides high sample throughput (96-well format), extensive sample clean-up, good sensitivity, and high reproducibility. The presented method is also the first method incorporating analysis of DBZD, BZD, and Z-hypnotics in whole blood in one efficient analysis. [Figure not available: see fulltext.].

AB - Benzodiazepines (BZD) and Z-hypnotics are frequently analyzed in forensic laboratories, and in 2012, the designer benzodiazepines (DBZD) emerged on the illegal drug scene. DBZD represent a particular challenge demanding new analytical methods. In this work, parallel artificial liquid membrane extraction (PALME) is used for sample preparation of DBZD, BZD, and Z-hypnotics in whole blood prior to UHPLC-MS/MS analysis. PALME of BZD, DBZD, and Z-hypnotics was performed from whole blood samples, and the analytes were extracted across a supported liquid membrane (SLM) and into an acceptor solution of dimethyl sulfoxide and 200 mM formic acid (75:25, v/v). The method was validated according to EMA guidelines. The method was linear throughout the calibration range (R2 > 0.99). Intra- and inter-day accuracy and precision, as well as matrix effects, were within the guideline limit of ± 15%. LOD and LLOQ ranged from 0.10 to 5.0 ng mL−1 and 3.2 to 160 ng mL−1, respectively. Extraction recoveries were reproducible and above 52%. The method was specific, and the analytes were stable in the PALME extracts for 4 and 10 days at 10 and − 20 °C. No carry-over was observed within the calibration range. PALME and UHPLC-MS/MS for the determination of DBZD, BZD, and Z-hypnotics in whole blood are a green and low-cost alternative that provides high sample throughput (96-well format), extensive sample clean-up, good sensitivity, and high reproducibility. The presented method is also the first method incorporating analysis of DBZD, BZD, and Z-hypnotics in whole blood in one efficient analysis. [Figure not available: see fulltext.].

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KW - Designer benzodiazepines

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KW - Parallel artificial liquid membrane extraction

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KW - Limit of Detection

KW - Tandem Mass Spectrometry/economics

KW - Humans

KW - Benzodiazepines/analysis

KW - Membranes, Artificial

KW - Equipment Design

KW - Designer Drugs/analysis

KW - Hypnotics and Sedatives/analysis

KW - Liquid-Liquid Extraction/economics

KW - Time Factors

KW - Chromatography, High Pressure Liquid/economics

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DO - 10.1007/s00216-018-1147-y

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SN - 1618-2642

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EP - 4978

JO - Analytical and Bioanalytical Chemistry

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IS - 20

ER -

Rapid determination of designer benzodiazepines, benzodiazepines, and Z-hypnotics in whole blood using parallel artificial liquid membrane extraction and UHPLC-MS/MS

Abstract

Keywords

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