A Fast and Validated High Throughput Bar Adsorptive Microextraction (HT-BAµE) Method for the Determination of Ketamine and Norketamine in Urine Samples
Abstract
1. Introduction
2. Results and Discussion
2.1. Optimization Procedure
2.2. Validation Assays
2.3. Figures of Merit
3. Materials and Methods
3.1. Chemicals, Sorbents and Samples
3.2. LVI-GC-MS(SIM) Instrumentation
3.3. Pre-Treatment of Urine Samples
3.4. HT-BAµE-µLD Methodology
3.5. Validation of HT-BAμE-μLD/LVI-GC-MS(SIM) Methodology
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Dinis-Oliveira, R.J. Metabolism and metabolomics of ketamine: A toxicological approach. Forensic Sci. Res. 2017, 2, 2–10. [Google Scholar] [CrossRef] [PubMed]
- Kuhar, M.J.; Liddle, H. Drugs of Abuse, 1st ed.; Marshall Cavendish Reference: New York, NY, USA, 2012; p. 173. [Google Scholar]
- de Bairros, A.V.; Lanaro, R.; de Almeida, R.M.; Yonamine, M. Determination of ketamine, norketamine and dehydronorketamine in urine by hollow-fiber liquid-phase microextraction using an essential oil as supported liquid membrane. Forensic Sci. Int. 2014, 243, 47–54. [Google Scholar] [CrossRef] [PubMed]
- World Drug Report 2019 (United Nations publication, Sales No. E.19.XI.8). Available online: https://wdr.unodc.org/wdr2019/ (accessed on 20 January 2020).
- Clements, J.A.; Nimmo, W.S. Pharmacokinetics and analgesic effect of ketamine in man. Br. J. Anaesth. 1981, 53, 27–30. [Google Scholar] [CrossRef] [PubMed]
- Karch, S. Pathology of Drug Abuse, 3rd ed.; CRC Press: Boca Raton, FL, USA, 2002; pp. 715–718. [Google Scholar]
- Adamowicz, P.; Kala, M. Urinary excretion rates of ketamine and norketamine following therapeutic ketamine administration: Method and detection window considerations. J. Anal. Toxicol. 2005, 29, 376–382. [Google Scholar] [CrossRef] [PubMed]
- Moore, K.A.; Sklerov, J.; Levine, B.; Jacobs, A.J. Urine concentrations of ketamine and norketamine following illegal consumption. J. Anal. Toxicol. 2001, 25, 583–588. [Google Scholar] [CrossRef] [PubMed]
- Lan, L.; Hu, B.; Yu, C. PH-resistant titania hybrid organic-inorganic coating for stir bar sorptive extraction of drugs of abuse in urine samples followed by high performance liquid chromatography-ultraviolet visible detection. J. Chromatogr. A 2010, 1217, 7003–7009. [Google Scholar] [CrossRef] [PubMed]
- Xiong, J.; Chen, J.; He, M.; Hu, B. Simultaneous quantification of amphetamines, caffeine and ketamine in urine by hollow fiber liquid phase microextraction combined with gas chromatography-flame ionization detector. Talanta 2010, 82, 969–975. [Google Scholar] [CrossRef] [PubMed]
- Cheng, P.S.; Fu, C.Y.; Lee, C.H.; Liu, C.; Chien, C.S. GC-MS quantification of ketamine, norketamine, and dehydronorketamine in urine specimens and comparative study using ELISA as the preliminary test methodology. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2007, 852, 443–449. [Google Scholar] [CrossRef] [PubMed]
- Moreno, I.; Barroso, M.; Martinho, A.; Cruz, A.; Gallardo, E. Determination of ketamine and its major metabolite, norketamine, in urine and plasma samples using microextraction by packed sorbent and gas chromatography-tandem mass spectrometry. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2015, 1004, 67–78. [Google Scholar] [CrossRef] [PubMed]
- Hasan, M.; Hofstetter, R.; Fassauer, G.M.; Link, A.; Siegmund, W.; Oswald, S. Quantitative chiral and achiral determination of ketamine and its metabolites by LC–MS/MS in human serum, urine and fecal samples. J. Pharm. Biomed. Anal. 2017, 139, 87–97. [Google Scholar] [CrossRef] [PubMed]
- Yang, C.A.; Liu, H.C.; Lin, D.L.; Liu, R.H.; Hsieh, Y.Z.; Wu, S.P. Simultaneous quantitation of methamphetamine, ketamine, opiates and their metabolites in urine by SPE and LC-MS-MS. J. Anal. Toxicol. 2017, 41, 679–687. [Google Scholar] [CrossRef] [PubMed]
- Anilanmert, B.; Çavuş, F.; Narin, I.; Cengiz, S.; Sertler, Ş.; Özdemir, A.A.; Açikkol, M. Simultaneous analysis method for GHB, ketamine, norketamine, phenobarbital, thiopental, zolpidem, zopiclone and phenytoin in urine, using C18 poroshell column. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2016, 1022, 230–241. [Google Scholar] [CrossRef] [PubMed]
- Brown, S.D.; Rhodes, D.J.; Pritchard, B.J. A validated SPME-GC-MS method for simultaneous quantification of club drugs in human urine. Forensic Sci. Int. 2007, 171, 142–150. [Google Scholar] [CrossRef] [PubMed]
- Ahmad, S.M.; Nogueira, J.M.F. High throughput bar adsorptive microextraction: A novel cost-effective tool for monitoring benzodiazepines in large number of biological samples. Talanta 2019, 199, 195–202. [Google Scholar] [CrossRef] [PubMed]
- Abujaber, F.; Ahmad, S.M.; Neng, N.R.; Rodríguez Martín-Doimeadios, R.C.; Guzmán Bernardo, F.J.; Nogueira, J.M.F. Bar adsorptive microextraction coated with multi-walled carbon nanotube phases—Application for trace analysis of pharmaceuticals in environmental waters. J. Chromatogr. A 2019, 1600, 17–22. [Google Scholar] [CrossRef] [PubMed]
- Ide, A.H.; Nogueira, J.M.F. New-generation bar adsorptive microextraction (BAμE) devices for a better eco-user-friendly analytical approach–Application for the determination of antidepressant pharmaceuticals in biological fluids. J. Pharm. Biomed. Anal. 2018, 153, 126–134. [Google Scholar] [CrossRef] [PubMed]
- Ahmad, S.M.; Ide, A.H.; Neng, N.R.; Nogueira, J.M.F. Application of bar adsorptive microextraction to determine trace organic micro-pollutants in environmental water matrices. Int. J. Environ. Anal. Chem. 2017, 97, 484–498. [Google Scholar] [CrossRef]
- Ahmad, S.M.; Gomes, M.I.; Ide, A.H.; Neng, N.R.; Nogueira, J.M.F. Monitoring traces of organochlorine pesticides in herbal matrices by bar adsorptive microextraction–Application to black tea and tobacco. Int. J. Environ. Anal. Chem. 2019, 1–15. [Google Scholar] [CrossRef]
Sample Availability: Not available. |
Analyte | Chemical Structure | log P 1 | pKa 1 | RT (min) | Ions (m/z) 2 |
---|---|---|---|---|---|
IS | - | - | 5.42 | 83, 168, 169 | |
NKET | 2.91 | 7.48 | 6.73 | 166, 168, 195 | |
KET | 3.35 | 7.45 | 6.97 | 180, 182, 209 |
Parameter | KET | NKET |
---|---|---|
LOD (μg L−1) | 1.0 | |
LLOQ (μg L−1) | 5.0 | |
Linear range (μg L−1) | 5.0 to 1000.0 | |
Calibration plot (n = 10) | y = 0.0032x + 0.0066 | y = 0.0032x + 0.029 |
r2 | 0.9990 | 0.9970 |
Intra-day assays (n = 6) | ||
5.0 μg L−1 | 87.2 ± 7.6 | 87.5 ± 11.9 |
50.0 μg L−1 | 87.4 ± 6.6 | 98.8 ± 5.5 |
200.0 μg L−1 | 87.9 ± 8.5 | 89.0 ± 6.8 |
1000.0 μg L−1 | 94.8 ± 3.2 | 98.6 ± 4.5 |
Inter-day assays (n = 18) | ||
5.0 μg L−1 | 110.0 ± 5.7 | 102.0 ± 12.6 |
50.0 μg L−1 | 104.4 ± 10.1 | 112.1 ± 11.8 |
200.0 μg L−1 | 94.7 ± 8.7 | 89.8 ± 12.3 |
1000.0 μg L−1 | 102.9 ± 6.9 | 85.5 ± 6.1 |
Recovery yields (n = 6) | ||
5.0 μg L−1 | 105.0 ± 9.2 | 103.1 ± 5.8 |
50.0 μg L−1 | 97.8 ± 7.9 | 89.8 ± 4.7 |
200.0 μg L−1 | 96.6 ± 7.2 | 88.1 ± 8.5 |
1000.0 μg L−1 | 96.5 ± 4.0 | 84.9 ± 3.4 |
Matrix effect (n = 6) | ||
5.0 μg L−1 | −4.4 ± 6.1 | 8.4 ± 6.3 |
50.0 μg L−1 | 4.9 ± 2.9 | −4.6 ± 10.4 |
200.0 μg L−1 | 9.0 ± 1.5 | 2.5 ± 14.1 |
1000.0 μg L−1 | −2.5 ± 6.2 | −9.1 ± 5.6 |
Microextraction Technique | HF-LPME | MEPS | SBSE | SPME | HF-LPME | HT-BAμE |
---|---|---|---|---|---|---|
Instrumental system | GC-MS | GC-MS/MS | HPLC-UV | GC-MS | GC-FID | LVI-GC-MS |
LODs(μg L−1) | 0.1–0.25 | 5 | 2.3–9.1 | 100 | 8 | 1.0 |
Linear range(μg L−1) | 0.5–50 | 10–250 | 30–3000 | 100–15000 | 3–350 | 5.0–1000.0 |
Accuracy (%) | 88.3–108 | 91.4–105.6 | n.a. | 105.9–113.6 | 75.2–119.3 | 85.5–112.1 |
Precision (%) | ≤10.1 | ≤9.2 | ≤8.9 | ≤14.8 | ≤8.9 | ≤12.6 |
Recovery (%) | 85.2–101 | 72.5–100.7 | 90.8 | n.a. | n.a. | 84.9–105.0 |
Sample volume (mL) | 2 | 0.25 | 3 | 1 | 3 | 0.5 |
Sample preparation time (min/sample) | 60 a | 7.42 b | 40 c | 21 d | 20 c | 45 |
Reference | [3] | [12] | [9] | [16] | [10] | This work |
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Ahmad, S.M.; Oliveira, M.N.; Neng, N.R.; Nogueira, J.M.F. A Fast and Validated High Throughput Bar Adsorptive Microextraction (HT-BAµE) Method for the Determination of Ketamine and Norketamine in Urine Samples. Molecules 2020, 25, 1438. https://doi.org/10.3390/molecules25061438
Ahmad SM, Oliveira MN, Neng NR, Nogueira JMF. A Fast and Validated High Throughput Bar Adsorptive Microextraction (HT-BAµE) Method for the Determination of Ketamine and Norketamine in Urine Samples. Molecules. 2020; 25(6):1438. https://doi.org/10.3390/molecules25061438
Chicago/Turabian StyleAhmad, Samir M., Mariana N. Oliveira, Nuno R. Neng, and J.M.F. Nogueira. 2020. "A Fast and Validated High Throughput Bar Adsorptive Microextraction (HT-BAµE) Method for the Determination of Ketamine and Norketamine in Urine Samples" Molecules 25, no. 6: 1438. https://doi.org/10.3390/molecules25061438
APA StyleAhmad, S. M., Oliveira, M. N., Neng, N. R., & Nogueira, J. M. F. (2020). A Fast and Validated High Throughput Bar Adsorptive Microextraction (HT-BAµE) Method for the Determination of Ketamine and Norketamine in Urine Samples. Molecules, 25(6), 1438. https://doi.org/10.3390/molecules25061438