Development and Validation of a Non-Targeted Screening Method for Most Psychoactive, Analgesic, Anaesthetic, Anti-Diabetic, Anti-Coagulant and Anti-Hypertensive Drugs in Human Whole Blood and Plasma Using High-Resolution Mass Spectrometry
Abstract
:1. Introduction
2. Results and Discussion
2.1. Optimisation
2.1.1. Chromatographic Conditions and Mass Spectrometer Parameters
2.1.2. Sample Pretreatment
2.1.3. Library
2.1.4. Screening Data Processing
2.2. Method Validation
2.2.1. Interference Studies
- 1.
- Selectivity
- 2.
- Specificity
- 3.
- Evaluating Interferences from Stable-Isotope Internal Standards and carry-over
- 4.
- Matrix effect
2.2.2. Recovery and Process Efficiency
2.2.3. Limit of Identification
2.2.4. Spectra Reproducibility
2.3. Applicability
3. Materials and Methods
3.1. Chemicals
3.2. Preparation of Stock Solutions and Working Solutions
3.3. Preparation of Quality Control Samples
3.4. Chromatographic and Mass Spectrometric Conditions
3.4.1. Liquid Chromatography
3.4.2. High-Resolution Mass Spectrometry
3.4.3. Screening Data Processing
- -
- for retention time, the option “ignore if not defined” was selected, and window override was 60 s;
- -
- for isotopic pattern, the fit threshold was 70 a.u., with a mass tolerance of 5 ppm and an intensity deviation tolerance of 30%;
- -
- for fragment ions, the option “ignore if not defined” was selected, the minimum number of fragments was one, the intensity threshold was 5000 a.u., the product mass tolerance was 10 mmu, and the MS order was MS²;
- -
- for general library NIST settings, MS order was MS² and isolation width was used; for the NIST setting, search type selected was MS/MS, and options “ignore precursor”, “use all peak matching”, “reverse search”, and presearch “off” were selected; a probability threshold of 10 a.u, score threshold of 80 a.u., search index (SI) threshold of 500 a.u., and reverse search index (RSI) threshold of 600 a.u. were selected; precursor and product masses tolerances were 5 ppm and 10 ppm, respectively; library score was selected as a passing value type with a passing value of 20 a.u.
3.4.4. Library
3.5. Sample Preparation
3.6. Validation Method
3.6.1. Interference Studies
- 1.
- Selectivity
- 2.
- Specificity
- 3.
- Evaluating Interferences from Stable-Isotope Internal Standards and carryover
- 4.
- Matrix effect
3.6.2. Recovery and Process Efficiency
3.6.3. Limit of Identification
3.6.4. Spectra Reproducibility
3.6.5. Statistics
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Compound Empirical Formula | RT (min) | m/z: Precursor Relative Abundances | m/z: Fragment Ion 1 Relative Abundances | m/z: Fragment Ion 2 Relative Abundances | m/z: Fragment Ion 3 Relative Abundances | m/z: Fragment Ion 4 Relative Abundances | m/z: Fragment Ion 5 Relative Abundances |
---|---|---|---|---|---|---|---|
O-Demethylvenlafaxine | 4.13 | 264.19581 | 58.06605 | 246.1852 | 107.04956 | 133.06494 | 201.1275 |
C16H25NO2 | 23.2 | 100 | 13.6 | 11.9 | 5.6 | 3.0 | |
Tramadol | 4.42 | 264.19581 | 58.06595 | 182.9018 | 246.1843 | 265.1989 | 56.0503 |
C16H25NO2 | 10.5 | 100 | 0.9 | 0.4 | 0.4 | 0.2 | |
MDEA | 3.79 | 208.13321 | 163.07542 | 135.04408 | 133.06488 | 105.07027 | 72.08154 |
C12H17NO2 | 15.2 | 100 | 33.4 | 31.4 | 31.3 | 9.5 | |
MBDB | 4.01 | 208.13321 | 135.04413 | 177.09102 | 147.08046 | 72.08154 | 136.0475 |
C12H17NO2 | 8.2 | 100 | 12.8 | 8.1 | 7.8 | 5.3 | |
Acepromazine | 6.02 | 327.15256 | 86.09708 | 58.06606 | 254.06337 | 239.0765 | 222.0916 |
C19H22N2OS | 50.2 | 100 | 73.3 | 8.5 | 4.0 | 3.6 | |
Aceprométazine | 5.94 | 327.15256 | 86.09696 | 240.04727 | 71.07362 | 239.07614 | 89.0602 |
C19H22N2OS | 14.8 | 100 | 20.3 | 6.8 | 5.8 | 2.5 | |
Morphine | 1.27 | 286.14377 | 201.09116 | 229.08565 | 183.08067 | 185.05997 | 211.07568 |
C17H19NO3 | 100 | 6.9 | 4.5 | 3.4 | 3.1 | 3.0 | |
Norcodeine | 2.95 | 286.14377 | 268.13263 | 215.10689 | 225.09088 | 121.06505 | 243.10130 |
C17H19NO3 | 100 | 10.7 | 6.5 | 5.4 | 5.3 | 4.7 | |
6-MAM | 3.56 | 328.15433 | 211.07524 | 165.06987 | 193.06425 | 58.06528 | 183.08049 |
C19H21NO4 | 100 | 13.1 | 7.5 | 7 | 6 | 4.5 | |
Naloxone | 3.11 | 328.15433 | 310.1438 | 253.10934 | 268.13297 | 311.14734 | 269.1049 |
C19H21NO4 | 75.4 | 100 | 22.3 | 19.5 | 11.6 | 10.3 | |
N-Demethylclobazam | 6.42 | 287.05818 | 245.04753 | 210.07864 | 241.05254 | 269.0474 | 246.0511 |
C15H11ClN202 | 29.2 | 100 | 13.7 | 12.4 | 4.8 | 2.7 | |
Oxazepam | 6.40 | 287.05818 | 241.05254 | 269.04745 | 104.04984 | 231.06830 | 128.02629 |
C15H11ClN202 | 40.4 | 100 | 40.9 | 17.6 | 15.3 | 8.7 |
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Feliu, C.; Konecki, C.; Cazaubon, Y.; Binet, L.; Vautier, D.; Fouley, A.; Gozalo, C.; Djerada, Z. Development and Validation of a Non-Targeted Screening Method for Most Psychoactive, Analgesic, Anaesthetic, Anti-Diabetic, Anti-Coagulant and Anti-Hypertensive Drugs in Human Whole Blood and Plasma Using High-Resolution Mass Spectrometry. Pharmaceuticals 2023, 16, 76. https://doi.org/10.3390/ph16010076
Feliu C, Konecki C, Cazaubon Y, Binet L, Vautier D, Fouley A, Gozalo C, Djerada Z. Development and Validation of a Non-Targeted Screening Method for Most Psychoactive, Analgesic, Anaesthetic, Anti-Diabetic, Anti-Coagulant and Anti-Hypertensive Drugs in Human Whole Blood and Plasma Using High-Resolution Mass Spectrometry. Pharmaceuticals. 2023; 16(1):76. https://doi.org/10.3390/ph16010076
Chicago/Turabian StyleFeliu, Catherine, Celine Konecki, Yoann Cazaubon, Laurent Binet, Damien Vautier, Aurélie Fouley, Claire Gozalo, and Zoubir Djerada. 2023. "Development and Validation of a Non-Targeted Screening Method for Most Psychoactive, Analgesic, Anaesthetic, Anti-Diabetic, Anti-Coagulant and Anti-Hypertensive Drugs in Human Whole Blood and Plasma Using High-Resolution Mass Spectrometry" Pharmaceuticals 16, no. 1: 76. https://doi.org/10.3390/ph16010076