Quantitative Determination of Four Potential Genotoxic Impurities in the Active Pharmaceutical Ingredients in TSD-1 Using UPLC-MS/MS
Abstract
:1. Introduction
2. Results and Discussion
2.1. Method Development
2.1.1. Optimization of Sample Preparation
2.1.2. Selection of Chromatographic Column and Separation
2.1.3. Optimization of Mass Spectrometric Parameters
2.2. Method Validation
2.2.1. Specificity
2.2.2. LOD, LOQ, and Linearity
2.2.3. Accuracy
2.2.4. Repeatability and Intermediate Precision
2.2.5. Solution Stability
2.2.6. Robustness
2.3. Analysis of TSD-1 API Batches
3. Materials and Methods
3.1. Chemicals and Reagents
3.2. Solutions for Method Validation
3.3. Chromatographic and Mass Spectrometric Conditions
3.4. Method Validation
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compound | Linear Range (ng/mL) | Calibration Curve Equation | Correlation Coefficient (R) | LOD (ng/mL) ± RSD (%) | LOQ (ng/mL) ± RSD (%) |
---|---|---|---|---|---|
PGI-1 | 0.1512–15.1158 | y = 642034x + 247551 | 0.9988 | 0.0453 ± 1.9 | 0.1512 ± 1.1 |
PGI-2 | 0.3844–15.3778 | y = 179172x + 52424 | 0.9981 | 0.1153 ± 2.5 | 0.3844 ± 1.4 |
PGI-3 | 0.3826–15.3046 | y = 100106x + 40037 | 0.9988 | 0.1148 ± 0.9 | 0.3826 ± 1.5 |
PGI-4 | 0.3897–15.5864 | y = 62612x + 24142 | 0.9971 | 0.1169 ± 1.4 | 0.3897 ± 2.8 |
Spike Level | PGI-1 | PGI-2 | PGI-3 | PGI-4 | |
---|---|---|---|---|---|
LOQ | Mean ± SD (%) | 94.9 ± 3.4 | 106.2 ± 4.7 | 111.4 ± 4.1 | 115.5 ± 2.8 |
RSD (%) | 3.6 | 4.4 | 3.7 | 2.4 | |
100% | Mean ± SD (%) | 101.3 ± 0.5 | 102.0 ± 1.4 | 100.0 ± 1.0 | 102.1 ± 0.6 |
RSD (%) | 0.5 | 1.4 | 1.0 | 0.6 | |
150% | Mean ± SD (%) | 98.6 ± 0.7 | 100.3 ± 1.9 | 100.3 ± 3.2 | 100.9 ± 0.5 |
RSD (%) | 0.7 | 1.9 | 3.2 | 0.5 |
Compound | PGI-1 | PGI-2 | PGI-3 | PGI-4 | |
---|---|---|---|---|---|
Analyst 1 | Mean ± SD (%) | 97.7 ± 1.5 | 111.4 ± 1.0 | 92.1 ± 1.1 | 97.5 ± 2.0 |
RSD (%) | 1.5 | 0.9 | 1.2 | 2.1 | |
Analyst 2 | Mean ± SD (%) | 98.6 ± 2.1 | 101.2 ± 3.4 | 97.8 ± 2.0 | 102.9 ± 3.3 |
RSD (%) | 2.1 | 3.3 | 2.1 | 3.2 |
Compound | Original Condition | Flow Rate (mL/min) | Column Temperature (°C) | Percentage of Acetonitrile (%) | Mean ± SD (%) | RSD (%) | |||
---|---|---|---|---|---|---|---|---|---|
0.28 | 0.32 | 28 | 32 | 18 | 22 | ||||
PGI-1 | 99.7 | 99.9 | 99.5 | 99.3 | 99.4 | 98.5 | 99.6 | 99.4 ± 0.5 | 0.5 |
PGI-2 | 112.5 | 107.1 | 123.0 | 127.6 | 112.5 | 97.8 | 96.2 | 111.0 ± 11.8 | 10.6 |
PGI-3 | 90.4 | 94.7 | 102.7 | 101.7 | 94.1 | 96.4 | 99.1 | 97.0 ± 4.4 | 4.6 |
PGI-4 | 94.3 | 106.2 | 99.8 | 99.5 | 106.4 | 107.6 | 102.0 | 102.3 ± 4.8 | 4.7 |
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Wang, T.; Yang, H.; Yang, J.; Guo, N.; Wu, G.; Xu, X.; An, M. Quantitative Determination of Four Potential Genotoxic Impurities in the Active Pharmaceutical Ingredients in TSD-1 Using UPLC-MS/MS. Molecules 2022, 27, 4129. https://doi.org/10.3390/molecules27134129
Wang T, Yang H, Yang J, Guo N, Wu G, Xu X, An M. Quantitative Determination of Four Potential Genotoxic Impurities in the Active Pharmaceutical Ingredients in TSD-1 Using UPLC-MS/MS. Molecules. 2022; 27(13):4129. https://doi.org/10.3390/molecules27134129
Chicago/Turabian StyleWang, Taiyu, Hailong Yang, Jie Yang, Ningjie Guo, Guodong Wu, Xueyu Xu, and Ming An. 2022. "Quantitative Determination of Four Potential Genotoxic Impurities in the Active Pharmaceutical Ingredients in TSD-1 Using UPLC-MS/MS" Molecules 27, no. 13: 4129. https://doi.org/10.3390/molecules27134129