Comparison of LC-MS and LC-DAD Methods of Detecting Abused Piperazine Designer Drugs
Abstract
:1. Introduction
2. Materials and Methods
2.1. Reagents and Solvents
2.2. Instrumentation
2.3. Chromatographic Conditions for LC-MS
2.4. Chromatographic Conditions for LC-DAD
2.5. LC-MS Analysis—Preparation of Calibration Samples
2.6. Biological Samples Preparation
2.7. LC-DAD Analysis—Preparation of Samples for Calibration
2.8. LC-DAD Analysis—Validation of the Method
2.9. LC-DAD Analysis—Linearity of the Method
2.10. LC-DAD Analysis—Analytical Limits
2.11. LC-DAD Analysis—Method Repeatability
3. Results
3.1. LC-MS Method—MRM Transitions and Chromatographic Separation
3.2. LC-DAD Method—UV-VIS Spectra and Chromatographic Separation
3.3. Validation of the LC-DAD Method (Measuring Range, Linearity, Repeatability, LOD and LOQ)
4. Discussion
4.1. LC-MS Method
4.2. LC-DAD Method
4.3. Comparison of LC-MS and LC-DAD Methods
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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PIPERAZINE | |
Benzylpiperazine Derivatives | Phenylpiperazine Derivatives |
BZP N-benzylpiperazine | mCPP 1-(3-chlorophenyl)piperazine |
MDBP 1-(3,4-methylenedioxybenzyl)piperazine | TFMPP 1-(3-trifluoromethylphenyl)piperazine |
pFBP 1-(4-fluorobenzyl)piperazine | pFPP 1-(4-parafluorophenyl)piperazine |
DBZP 1,4-dibenzylpiperazine | MeOPP 1-(4-methoxyphenyl)piperazine |
Compound | Precursor Ion (m/z) | Fragmentation Patterns (m/z) | ||
---|---|---|---|---|
BZP | 177.3 | 90.95 | 64.95 | 86 |
C11H16N2 | [C11H16N2]+ | [C7H7]+ | [C5H5]+ | [C4H10N2] |
MDBP | 135.00 | 76.9 | 86 | |
C12H16N202 | [C12H16N202]+ | [C8H7O2]+ | [C6H5]+ | [C4H10N2] |
pFBP | 195 | 108.90 | 83.00 | 86 |
C11H15FN2 | [C11H15FN2]+ | [C7H6F]+ | [C5H4F]+ | [C4H10N2] |
mCPP | 197.05 | 153.95 | 117.95 | 44 |
C10H13ClN2 | [C10H13ClN2]+ | [C8H9ClN]+ | [C8H8N]+ | [C2H5N]+ |
TFMPP | 187.95 | 118.10 | 44 | |
C11H13F3N2 | [C11H13F3N2]+ | [C9H9F3N]+ | [C8H8N]+ | [C2H5N]+ |
Compound Name | Mobile Phase Composition: BF70/MeOH20/ACN10 | |||||
---|---|---|---|---|---|---|
BF 20 mM | BF 100 mM | |||||
tR (pH 2.7) | tR (pH 3.6) | tR (pH 4.1) | tR (pH 4.6) | tR (pH 6.0) | tR (pH 6.0) | |
BPZ | 3.036 | 3.659 | 3.832 | 3.857 | 4.032 | 3.985 |
MDBP | 3.065 | 3.775 | 3.979 | 4.009 | 4.187 | 4.135 |
pFBP | 3.359 | 4.192 | 4.392 | 4.423 | 4.632 | 4.560 |
mCPP | 5.215 | 5.235 | 5.309 | 5.320 | 5.736 | 5.591 |
TFMPP | 8.216 | 8.249 | 8.368 | 8.561 | 9.707 | 9.382 |
Compound Name | Mobile Phase Composition: BF85/MeOH10/ACN5 | ||||
---|---|---|---|---|---|
BF 20 mM | BF 100 mM | ||||
tR (pH 3.6) | tR (pH 4.1) | tR (pH 4.6) | tR (pH 6.0) | tR (pH 6.0) | |
BPZ | 4.996 | 5.702 | 6.024 | 6.472 | 6.588 |
MDBP | 5.437 | 6.438 | 6.859 | 7.477 | 7.534 |
pFBP | 6.417 | 7.380 | 7.775 | 8.340 | 8.433 |
mCPP | 11.763 | 11.835 | 12.015 | 12.654 | 12.791 |
TFMPP | 23.663 | 23.680 | 24.569 | 26.783 | 27.257 |
Analytes | Internal Standard | Linear Range (ng/mL) | Regression Equation | R2 | Analytes LOD (ng/mL) | Analytes LOQ (ng/mL) |
---|---|---|---|---|---|---|
BZP | Pentedrone | 500–7000 | y = 0.0001x − 0.0235 | 0.9984 | 150 | 450 |
MDBP | Pentedrone | 500–7000 | y = 0.0006x − 0.0397 | 0.9917 | 110 | 330 |
pFBP | Pentedrone | 500–7000 | y = 0.0027x − 0.3238 | 0.9941 | 100 | 300 |
mCPP | Pentedrone | 500–7000 | y = 0.0005x + 0.0645 | 0.9919 | 150 | 450 |
TFMPP | Pentedrone | 500–7000 | y = 0.0006x − 0.0884 | 0.9961 | 140 | 420 |
Analytes | Level | Daily Accuracy for tR, n = 12 CV (%) | Daily Accuracy for AUC, n = 12 CV (%) | Accuracy between Days for tR CV (%) | Accuracy between Days for AUC CV (%) |
---|---|---|---|---|---|
BPZ | LQC | 0.24 | 1.42 | 0.64 | 9.64 |
MQC | 0.14 | 1.18 | 0.49 | 5.04 | |
HQC | 0.12 | 1.56 | 0.44 | 7.75 | |
MDBP | LQC | 0.23 | 3.12 | 0.38 | 4.06 |
MQC | 0.14 | 2.20 | 0.47 | 3.51 | |
HQC | 0.11 | 1.20 | 0.40 | 5.07 | |
pFBP | LQC | 0.11 | 1.74 | 0.26 | 10.31 |
MQC | 0.03 | 0.76 | 0.05 | 5.73 | |
HQC | 0.07 | 1.92 | 0.11 | 1.69 | |
mCPP | LQC | 0.04 | 0.95 | 1.32 | 2.24 |
MQC | 0.04 | 1.07 | 1.27 | 1.20 | |
HQC | 0.04 | 1.00 | 1.34 | 2.47 | |
TFMPP | LQC | 0.05 | 2.34 | 0.84 | 4.65 |
MQC | 0.34 | 1.13 | 1.26 | 3.11 | |
HQC | 0.04 | 1.20 | 1.44 | 3.47 |
Identification of Piperazine Designer Drug in Urine | Identification of Piperazine Designer Drugs in Serum |
---|---|
Analytes | Internal Standard | Urine | Serum | ||||
---|---|---|---|---|---|---|---|
Average 1000 ng | Standard Deviation | %CV | Average 1000 ng | Standard Deviation | %CV | ||
BPZ | BZP-D7 | 1183.70 | 14.47 | 1.18 | 1120.88 | 9.71 | 0.87 |
MDBP | BZP-D7 | 1021.15 | 7.70 | 0.75 | 983.20 | 11.25 | 1.14 |
pFBP | BZP-D7 | 973.34 | 13.08 | 1.34 | 1006.45 | 16.52 | 1.64 |
mCPP | mCPP-D8 | 1095.33 | 8.11 | 0.74 | 1146.73 | 18.71 | 1.63 |
TFMPP | TFMPP-D4 | 996.96 | 1.61 | 0.16 | 1013.00 | 27.61 | 2.73 |
Elements of the Measuring System and Work Parameters | LC-MS Method | LC-DAD Method |
---|---|---|
Liquid chromatograph | LCMS-8045, Shimadzu | LC-DAD, Shimadzu |
Mobile phase | A: Water (0.1%FA) B: Methanol (0.1%FA) | A: 20 mM phosphate buffer B: Acetonitrile C: Methanol |
Column | Synergi Hydro-RP C18 4 μm; 2.00 × 150 mm | Xterra RP C18 5 μm; 4.6 × 150 mm |
Injection volume | 5 μL | 10 μL |
Analysis time | 15 min | 20 min |
Compound | Mass Spectra from LC-MS | UV/VIS Spectra from LC-DAD |
---|---|---|
BZP | ||
MDBP | ||
pFBP | ||
mCPP | ||
TFMPP |
General Name of Therapeutic Drug | Pharmacological Classification | Piperazine Derivatives as Metabolite | References |
---|---|---|---|
Antrafenine | Analgesic | TFMPP | [17,53,54] |
Trazodone | Antidepressant | mCPP | [57,58,59,60,62] |
Nefazodone | Antidepressant | mCPP | [10,26] |
Etoperidone | Antidepressant | mCPP | [10,26] |
Enziprazole | Antidepressant | mCPP | [10,26] |
Mepiprazole | Tranquilizer | mCPP | [10,26,56] |
Urapidil | Antihypertensive | MeOPP | [26,65] |
Fipexide (withdrawn from the treatment) | Nootropic | MDBP | [66,67] |
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Welz, A.; Koba, M.; Kośliński, P.; Siódmiak, J. Comparison of LC-MS and LC-DAD Methods of Detecting Abused Piperazine Designer Drugs. J. Clin. Med. 2022, 11, 1758. https://doi.org/10.3390/jcm11071758
Welz A, Koba M, Kośliński P, Siódmiak J. Comparison of LC-MS and LC-DAD Methods of Detecting Abused Piperazine Designer Drugs. Journal of Clinical Medicine. 2022; 11(7):1758. https://doi.org/10.3390/jcm11071758
Chicago/Turabian StyleWelz, Anna, Marcin Koba, Piotr Kośliński, and Joanna Siódmiak. 2022. "Comparison of LC-MS and LC-DAD Methods of Detecting Abused Piperazine Designer Drugs" Journal of Clinical Medicine 11, no. 7: 1758. https://doi.org/10.3390/jcm11071758
APA StyleWelz, A., Koba, M., Kośliński, P., & Siódmiak, J. (2022). Comparison of LC-MS and LC-DAD Methods of Detecting Abused Piperazine Designer Drugs. Journal of Clinical Medicine, 11(7), 1758. https://doi.org/10.3390/jcm11071758