28 February / March 2017 References
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-0 -0
100 200 300 400 500
-0 -0 300 Nitrazepam 200 100 Conc 50 100150 200 250 300 350400 450500 -0 -0 Diazepam
1. Jufer-Phipps, R., B. Levine: Benzodiazepines. In: Principles of Forensic Toxicology, B. Levine (Eds). AACC Press, Washington, D.C. 237-270 (2013).
Conc 50 100150 200 250 300 350400 450500
2. Karithanom, M. Number of Deaths from Prescription Drugs, National Institute of Drug Abuse, National Overdose Deaths, CDC Wonder, (2015). https://www.
drugabuse.gov/related-topics/trends- statistics/overdose-death-rates
Alprazolam
100 200 300 400
Conc 50 100150 200250 300 350 400 450 500 -0 -0 7-aminoclonazepam Conc 50 100 150200 250300 350400 450 500
Figure 4. Representative calibration curves of benzodiazepines. Nitrazepam and alprazolam were fit with a 1/x weighted line, while diazepam and 7-aminoclonazepam were best fit with a quadratic 1/x weighted curve.
results for a wide range of analytes in a single run. This approach significantly reduces analysis time when compared to immunoassays or single-analyte methods. Using a water-wettable SPE sorbent eliminates the common conditioning and equilibration steps associated with conventional methods without any loss in recovery or reproducibility. This property also enables the entire hydrolysis step to be
conducted within the wells of the µElution plate, eliminating time consuming and error-prone transfer steps, reducing the total number of post-incubation steps from nine to five. Combining this extraction procedure with the high efficiency separation capabilities of a solid-core UPLC column, results in a rapid, efficient and exceptionally accurate analytical method.
3. Laloup, M., M.d.M.R. Fernandez, G. De Boeck, M. Wood, V. Maes, N. Samyn: Validation of a Liquid Chromatography- Tandem Mass Spectrometry Method for the Simultaneous Determination of 26 Benzodiazepines and Metabolites, Zolpidem and Zopiclone, in Blood, Urine, and Hair. Journal of Analytical Toxicology 29(7), 616-626 (2005).
4. Marin, S.J., R. Coles, M. Merrell, G.A. McMillin: Quantitation of Benzodiazepines in Urine, Serum, Plasma, and Meconium by LC-MS-MS. Journal of Analytical Toxicology 32(7), 491-498 (2008).
5. Marin, S.J., M. Roberts, M. Wood, G.A. McMillin: Sensitive UPLC–MS-MS Assay for 21 Benzodiazepine Drugs and Metabolites, Zolpidem and Zopiclone in Serum or Plasma. Journal of Analytical Toxicology 36(7), 472-476 (2012).
Table 4. Between-batch QC results. Values represent the mean accuracy and %CV of separate extraction batches. Mean values show the average accuracy for each compound and the average accuracy for all compounds at each QC level.
QC 1.5 Name
N-desmethyl zopiclone Zopiclone Zolpidem
7-aminoclonazepam Flurazepam
7-aminoflunitrazepam Chlordiazepoxide Midazolam
α-OH midazolam α-OH triazolam α-OH alprazolam Oxazepam Nitrazepam Lorazepam Clonazepam Alprazolam
Nordiazepam Flunitrazepam Temazepam Triazolam Diazepam Mean
100.4% 103.6% 99.3%
100.5% 103.7% 103.4% 101.5% 104.4% 100.4% 102.0% 100.3% 102.0% 107.0% 106.1% 101.8% 102.9% 104.4% 104.3% 102.1%
3.8% 3.2% 3.4% 1.9% 7.1% 2.3% 1.1% 4.4% 4.3% 8.4% 9.6% 4.3% 6.2% 6.9% 4.9% 8.7% 9.0% 8.1% 7.3% 8.4% 6.5%
QC 7.5
96.7% 96.7% 98.8% 95.6% 97.6% 93.7%
100.3% 104.2% 102.5% 98.8%
101.4% 98.5% 95.8%
100.2% 98.2% 94.6%
106.7% 98.2%
101.6% 102.4% 103.8% 99.3%
2.4% 3.4% 1.5% 1.0% 4.3% 2.3% 2.1% 5.4% 4.7% 4.9% 2.2% 4.1% 1.3% 4.2% 3.0% 4.7% 3.7% 2.8% 1.2% 2.3% 2.1%
96.6% 98.0% 95.8% 93.8% 99.3% 96.1% 99.3%
QC 75
102.1% 100.8% 98.3% 99.1% 98.2% 95.7%
100.8% 97.5% 95.0%
101.7% 96.3% 97.5% 99.9% 99.6% 98.2%
2.9% 2.8% 1.1% 2.4% 7.4% 4.7% 1.5% 3.1% 5.0% 4.9% 5.9% 4.7% 2.4% 5.4% 3.3% 4.6% 4.6% 2.6% 2.8% 3.2% 4.1%
QC 300
Mean %CV Mean %CV Mean %CV Mean %CV Mean 99.2% 97.7% 99.4%
97.1% 96.2% 91.7% 95.1% 97.6% 97.0% 98.4% 98.9% 99.1% 95.1% 97.7% 97.6% 98.1% 98.7% 95.2% 98.8% 95.4% 96.3% 94.7% 98.2% 94.9% 96.8%
4.7% 3.5% 1.6% 2.0% 5.0% 3.2% 3.2% 2.0% 2.5% 2.6% 2.4% 4.6% 1.8% 4.9% 4.5% 4.5% 5.2% 7.8% 1.8% 3.4% 7.6%
97.4% 97.2% 96.4% 96.2% 99.5% 96.5% 99.6%
102.2% 101.4% 98.4%
100.7% 98.7% 97.9%
100.0% 98.2% 98.9%
102.5% 98.1% 99.2%
101.2% 100.6%
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