Development of a Fast and Robust UHPLC Method for Apixaban In-Process Control Analysis
Abstract
:1. Introduction
2. Results
2.1. Sample
2.2. Liquid Chromatographic Method Development
- -
- = 1.5 min; = 4.5 min / = 20 C; = 80 C / pH = 2.8; pH = 4.0; pH = 5.2
- -
- = 1.5 min; = 4.5 min / = 20 C; = 50 C / pH = 2.8; pH = 4.6; pH = 6.4
2.3. Robustness Testing
3. Materials and Methods
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
Abbreviations
DOAJ | Directory of open access journals |
ACN | Acetonitrile |
API | Active Pharmaceutical Ingredient |
DoE | Design of Experiment |
HPLC | High-Performance Liquid Chromatography |
IPC | In-Process Control |
QbD | Quality by Design |
RPLC | Reversed Phase Liquid Chromatography |
UHPLC | Ultra-High-Performance Liquid Chromatography |
References
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Stm1 | Int1 | Int2 | Stm2 | Int3 | Int4 | Int5 | Int6 | Apixaban | |
---|---|---|---|---|---|---|---|---|---|
Stm1 | 1.00 | 0.87 | 0.64 | — | 0.92 | 1.13 | 0.90 | 0.98 | 1.16 |
Int1 | — | 1.00 | 0.73 | — | 1.06 | 1.30 | 1.03 | 1.13 | 1.34 |
Int2 | — | — | 1.00 | — | 1.44 | 1.77 | 1.41 | 1.54 | 1.82 |
Stm2 | — | — | — | 1.00 | 1.88 | 2.32 | 1.84 | 2.01 | 2.38 |
Int3 | — | — | — | — | 1.00 | 1.23 | 0.98 | 1.07 | 1.27 |
Int4 | — | — | — | — | — | 1.00 | 0.79 | 0.87 | 1.03 |
Int5 | — | — | — | — | — | — | 1.00 | 1.09 | 1.29 |
Int6 | — | — | — | — | — | — | — | 1.00 | 1.19 |
Apixaban | — | — | — | — | — | — | — | — | 1.00 |
OP | 637 | 396 | 390 | 638 | 611 | 584 | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Pred. | Exp. | Pred. | Exp. | Pred. | Exp. | Pred. | Exp. | Pred. | Exp. | Pred. | Exp. | Pred. | Exp. | |
Int6 | 0.88 | 0.89 | 0.83 | 0.83 | 0.93 | 0.94 | 0.89 | 0.89 | 0.82 | 0.83 | 0.82 | 0.83 | 0.82 | 0.82 |
Stm1 | 1.13 | 1.13 | 1.05 | 1.04 | 1.16 | 1.16 | 1.12 | 1.12 | 1.04 | 1.03 | 1.04 | 1.04 | 1.04 | 1.03 |
Apixaban | 1.32 | 1.32 | 1.22 | 1.21 | 1.40 | 1.40 | 1.36 | 1.36 | 1.21 | 1.22 | 1.21 | 1.22 | 1.21 | 1.21 |
Int2 | 1.43 | 1.44 | 1.31 | 1.31 | 1.48 | 1.46 | 1.44 | 1.42 | 1.30 | 1.30 | 1.30 | 1.32 | 1.30 | 1.31 |
Int1 | 1.69 | 1.69 | 1.54 | 1.55 | 1,76 | 1.75 | 1.72 | 1.72 | 1.53 | 1.53 | 1.53 | 1.53 | 1.53 | 1.53 |
Int5 | 1.85 | 1.85 | 1.69 | 1.67 | 1.96 | 1.98 | 1.93 | 1.94 | 1.67 | 1.68 | 1.67 | 1.68 | 1.67 | 1.67 |
Stm2 | 1.96 | 1.96 | 1.78 | 1.77 | 2.06 | 2.05 | 2.03 | 2.05 | 1.77 | 1.79 | 1.77 | 1.78 | 1.77 | 1.78 |
Int4 | 2.16 | 2.16 | 1.96 | 1.95 | 2.30 | 2.30 | 2.28 | 2.29 | 1.94 | 1.95 | 1.94 | 1.94 | 1.94 | 1.95 |
Int3 | 2.22 | 2.22 | 2.01 | 1.98 | 2.35 | 2.37 | 2.33 | 2.34 | 1.99 | 2.00 | 1.99 | 1.99 | 1.99 | 1.99 |
Int4-Int3 | 2.40 | 2.37 | 2.27 | 2.24 | 2.27 | 2.25 | 2.27 | 2.24 | 2.27 | 2.23 | 2.27 | 2.23 | 2.27 | 2.23 |
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Kormány, R.; Rácz, N.; Fekete, S.; Horváth, K. Development of a Fast and Robust UHPLC Method for Apixaban In-Process Control Analysis. Molecules 2021, 26, 3505. https://doi.org/10.3390/molecules26123505
Kormány R, Rácz N, Fekete S, Horváth K. Development of a Fast and Robust UHPLC Method for Apixaban In-Process Control Analysis. Molecules. 2021; 26(12):3505. https://doi.org/10.3390/molecules26123505
Chicago/Turabian StyleKormány, Róbert, Norbert Rácz, Szabolcs Fekete, and Krisztián Horváth. 2021. "Development of a Fast and Robust UHPLC Method for Apixaban In-Process Control Analysis" Molecules 26, no. 12: 3505. https://doi.org/10.3390/molecules26123505