Uncertainty Evaluation for the Quantification of Urinary Amphetamine and 4-Hydroxyamphetamine Using Liquid Chromatography–Tandem Mass Spectrometry: Comparison of the Guide to the Expression of Uncertainty in Measurement Approach and the Monte Carlo Method with R
Abstract
:1. Introduction
2. Results and Discussion
2.1. GUM Approach for Evaluating the Measurement Uncertainty
2.1.1. Urine Sample Dilution
2.1.2. Preparation of Calibrators
2.1.3. Calibration Curve
2.1.4. Method Repeatability
2.1.5. Calculating the Combined and Expanded Uncertainty
2.2. MCM for the Evaluation of MU
2.2.1. Mathematical Modeling of the Measurand
2.2.2. MCM Simulation
2.2.3. Uncertainty with MCM and Comparison with GUM Approach
3. Materials and Methods
3.1. Chemicals and Reagents
3.2. Preparation of Urine Sample
3.3. Preparation of Calibrators and QC Samples
3.4. LC–MS/MS Conditions
3.5. Identification of the Uncertainty Sources
3.6. Uncertainty Estimation Method
3.7. Specifying the Measurand
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Quantity | Unit | Value | Standard Uncertainty | Probability Density Function |
---|---|---|---|---|
mg/mL | 1.00 | 0.003 | Normal (1.00, ) | |
mL | 10 | 0.003 | Normal (10, | |
°C | - | 0.04301 | Uniform (−0.0745, 0.0745) | |
μL | 1000 | 0.75 | Normal (1000, ) | |
μL | 500 | 0.75 | Normal (500, ) | |
μL | 100 | 0.1 | Normal (100, ) | |
μL | 50 | 0.1 | Normal (50, ) |
Analyte | Nominal Concentration (ng/mL) | Experiments | |||||||
---|---|---|---|---|---|---|---|---|---|
Assay 1 | Assay 2 | Assay 3 | Assay 4 | ||||||
Mean (n = 6) | Standard Deviation | Mean (n = 6) | Standard Deviation | Mean (n = 6) | Standard Deviation | Mean (n = 6) | Standard Deviation | ||
AP | 30 | 32.3 | 0.4176 | 32.9 | 0.4840 | 29.3 | 0.3014 | 31.5 | 0.8831 |
150 | 165.4 | 2.7589 | 160.4 | 1.5858 | 144.5 | 4.3782 | 155.9 | 3.3410 | |
300 | 308.7 | 3.6577 | 314.9 | 5.2759 | 288.8 | 4.2205 | 303.4 | 2.7928 | |
4HA | 6 | 6.7 | 0.1797 | 6.6 | 0.1135 | 5.8 | 0.1940 | 6.5 | 0.2496 |
30 | 32.9 | 0.4256 | 33.6 | 0.6306 | 30.2 | 0.6749 | 31.4 | 0.9422 | |
150 | 163.2 | 3.5016 | 163.2 | 2.2802 | 145.3 | 2.5725 | 151.3 | 3.1556 |
Source of Uncertainty | AP | 4HA | ||||
---|---|---|---|---|---|---|
Relative Standard Uncertainty | Effective Degrees of Freedom | Degree of Contribution (%) | Relative Standard Uncertainty | Effective Degrees of Freedom | Degree of Contribution (%) | |
Urine sample dilution () | 0.000866 | ∞ | 0.05 | 0.000866 | ∞ | 0.03 |
Preparation of calibrators () | 0.018953 | ∞ | 25.98 | 0.019036 | ∞ | 16.05 |
Calibration curve () | 0.025458 | 5 | 46.87 | 0.032891 | 5 | 47.92 |
Method repeatability () | 0.019355 | 55 | 27.09 | 0.028505 | 51 | 35.99 |
Relative combined standard uncertainty () | 0.037184 | 22 | - | 0.047512 | 21 | - |
Relative expanded uncertainty () | 0.076971 | - | - | 0.098826 | - | - |
Statistical Data | AP | 4HA | ||
---|---|---|---|---|
GUM | MCM | GUM | MCM | |
Mean (ng/mL) | 99.74 | 99.75 | 11.33 | 11.33 |
Standard deviation (ng/mL) | 3.71 | 2.53 | 0.54 | 0.41 |
95% confidence interval (ng/mL) | (92.06, 107.41) | (94.83, 104.74) | (10.21, 12.45) | (10.52, 12.14) |
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Kim, S.Y.; Shin, D.W.; Hyun, J.; Kwon, N.H.; Cheong, J.C.; Paeng, K.-J.; Lee, J.; Kim, J.Y. Uncertainty Evaluation for the Quantification of Urinary Amphetamine and 4-Hydroxyamphetamine Using Liquid Chromatography–Tandem Mass Spectrometry: Comparison of the Guide to the Expression of Uncertainty in Measurement Approach and the Monte Carlo Method with R. Molecules 2023, 28, 6803. https://doi.org/10.3390/molecules28196803
Kim SY, Shin DW, Hyun J, Kwon NH, Cheong JC, Paeng K-J, Lee J, Kim JY. Uncertainty Evaluation for the Quantification of Urinary Amphetamine and 4-Hydroxyamphetamine Using Liquid Chromatography–Tandem Mass Spectrometry: Comparison of the Guide to the Expression of Uncertainty in Measurement Approach and the Monte Carlo Method with R. Molecules. 2023; 28(19):6803. https://doi.org/10.3390/molecules28196803
Chicago/Turabian StyleKim, Seon Yeong, Dong Won Shin, Jihye Hyun, Nam Hee Kwon, Jae Chul Cheong, Ki-Jung Paeng, Jooyoung Lee, and Jin Young Kim. 2023. "Uncertainty Evaluation for the Quantification of Urinary Amphetamine and 4-Hydroxyamphetamine Using Liquid Chromatography–Tandem Mass Spectrometry: Comparison of the Guide to the Expression of Uncertainty in Measurement Approach and the Monte Carlo Method with R" Molecules 28, no. 19: 6803. https://doi.org/10.3390/molecules28196803
APA StyleKim, S. Y., Shin, D. W., Hyun, J., Kwon, N. H., Cheong, J. C., Paeng, K. -J., Lee, J., & Kim, J. Y. (2023). Uncertainty Evaluation for the Quantification of Urinary Amphetamine and 4-Hydroxyamphetamine Using Liquid Chromatography–Tandem Mass Spectrometry: Comparison of the Guide to the Expression of Uncertainty in Measurement Approach and the Monte Carlo Method with R. Molecules, 28(19), 6803. https://doi.org/10.3390/molecules28196803