Advantages and Pitfalls of Capillary Electrophoresis of Pharmaceutical Compounds and Their Enantiomers in Complex Samples: Comparison of Hydrodynamically Opened and Closed Systems
Abstract
:1. Introduction
2. Results and Discussion
2.1. Comparison of Hydrodynamically Opened and Closed Separation Systems
2.1.1. Repeatability
2.1.2. Efficiency and Resolution
2.1.3. Sensitivity
2.2. Comparison of Hydrodynamically Opened and Closed Separation Systems for Chiral Separations
2.3. Comparison of Hydrodynamically Opened and Closed Separation Systems for Analysis of Pharmaceuticals in Serum Samples
3. Materials and Methods
3.1. Instrumentation and Software
3.2. Chemicals and Reagents
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
CE | Capillary electrophoresis |
EOF | Electroosmotic flow |
HPLC | High-performance liquid chromatography |
i.d. | Internal diameter |
LOD | Limit of detection |
CSS | Hydrodynamically closed separation system with suppressed electroosmotic flow |
OSS | Hydrodynamically opened separation system |
µep | Electrophoretic mobility |
HDF | Hydrodynamic flow |
PPL | Propranolol |
PDL | Pindolol |
OSS-EOF | Hydrodynamically opened separation system with electroosmotic flow |
OSS-sEOF | Hydrodynamically opened separation system with suppressed electroosmotic flow |
MHEC | Methylhydroxyethylcelullose |
DETA | Diethylenetriamine |
Vinj | Injected volume |
d | Capillary diameter |
API | Active pharmaceutical ingredient |
LOQ | Limit of quantitation |
UHPLC | Ultra high-performance liquid chromatography |
CMBCD | Carboxymethyl-β-cyclodextrin |
µEOF | Electroosmotic mobility |
µCD | Electrophoretic mobility of chiral selector |
µCD,eff | Effective mobility of chiral selector |
CEBCD | Carboxyethyl-β-cyclodextrin |
ΔµCD | Reduction of electrophoretic mobility due to chiral selector |
o.d. | Outer diameter |
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Parameter | OSS-EOF | OSS-sEOF | CSS | |||
---|---|---|---|---|---|---|
PDL | PPL | PDL | PPL | PDL | PPL | |
µep × 108 (m2V−1s−1) | 1.74 | 1.66 | 1.83 | 1.75 | 2.52 | 2.37 |
RSD tm (%) | 0.3 | 0.3 | 0.4 | 0.4 | 0.5 | 0.5 |
RSD A (%) | 2.0 | 1.4 | 3.4 | 2.4 | 2.2 | 1.6 |
N × 10−3 (m−1) | 309 | 310 | 465 | 482 | 162 | 147 |
LOD (µmol/L) | 1.20 | 1.10 | 1.50 | 1.40 | 0.06 | 0.07 |
Resolution (1) | 1.47 | 3.64 | 3.23 |
Required LOD | Achieved LOD (µmol/L) | ||||||||
---|---|---|---|---|---|---|---|---|---|
% (w/w) | mg/mL | µmol/L | OSS-EOF | OSS-sEOF | CSS | ||||
PDL | PPL | PDL | PPL | PDL | PPL | PDL | PPL | ||
0.02 | 2.0 × 10−5 | 0.08 | 0.08 | 1.20 | 1.10 | 1.50 | 1.40 | 0.06 | 0.07 |
Chiral Selector | OSS-EOF | OSS-sEOF | CSS | |||
---|---|---|---|---|---|---|
PDL | PPL | PDL | PPL | PDL | PPL | |
CMBCD | Rs = 1.33 | Rs = 1.42 | Rs = 5.22 | r.m. | Rs = 2.06 | n.t. |
CEBCD | n.t. | n.t. | n.t. | n.t. | n.t. | Rs = 1.36 |
System | PDLen1 | PDLen2 | PPLen1 | PPLen2 | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
µeof | µep | µeff | µCD (1) | µeff | µCD | µep | µeff | µCD (1) | µeff | µCD | |
OSS-EOF | +2.20 | +1.74 | +2.60 | −1.34 | +2.56 | −1.38 | +1.66 | +1.74 | −2.12 | +1.69 | −2.17 |
OSS-sEOF | 0 | +1.83 | +0.59 | −1.24 | +0.55 | −1.28 | +1.75 | −0.37 | −2.12 | −0.42 | −2.17 |
CSS | 0 | +2.52 | +1.18 | −1.34 | +1.12 | −1.40 | +2.37 | +1.08 (2) | −1.29 (2) | +1.05 (2) | −1.32 (2) |
Parameter | OSS-sEOF | CSS | ||
---|---|---|---|---|
PDL | PPL | PDL | PPL | |
µep × 108 (m2V−1s−1) | 1.75 | 1.66 | 2.50 | 2.36 |
RSD tm (%) | 0.3 | 0.3 | 0.8 | 0.8 |
RSD A (%) | 2.0 | 1.4 | 1.7 | 3.0 |
N × 10−3 (m−1) | 392 | 410 | 151 | 124 |
LOD (µmol/L) | 3.4 | 3.2 | 0.08 | 0.08 |
Resolution | 3.78 | 2.73 |
Chiral Selector | OSS-EOF | OSS-sEOF | CSS | |||
---|---|---|---|---|---|---|
PDL | PPL | PDL | PPL | PDL | PPL | |
CMBCD | Rs = 1.16 | r.m. | Rs = 2.68 | n.t. | Rs = 1.46 | n.t. |
CEBCD | n.t. | n.t. | n.t. | n.t. | n.t. | Rs = 1.04 |
Chiral | Analyte | OSS-sEOF | CSS | ||
---|---|---|---|---|---|
Selector | µeff × 108 (m2V−1s−1) | µeff × 108 (m2V−1s−1) | |||
Model Sample | Spiked Serum | Model Sample | Spiked Serum | ||
CMBCD | PDLen1 | 0.59 | 0.96 | 1.18 | 2.10 |
PDLen2 | 0.55 | 0.93 | 1.12 | 2.03 | |
CEBCD | PPLen1 | r.m. | n.t. | 1.08 | 1.99 |
PPLen2 | r.m. | n.t. | 1.05 | 1.94 |
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Masár, M.; Hradski, J.; Schmid, M.G.; Szucs, R. Advantages and Pitfalls of Capillary Electrophoresis of Pharmaceutical Compounds and Their Enantiomers in Complex Samples: Comparison of Hydrodynamically Opened and Closed Systems. Int. J. Mol. Sci. 2020, 21, 6852. https://doi.org/10.3390/ijms21186852
Masár M, Hradski J, Schmid MG, Szucs R. Advantages and Pitfalls of Capillary Electrophoresis of Pharmaceutical Compounds and Their Enantiomers in Complex Samples: Comparison of Hydrodynamically Opened and Closed Systems. International Journal of Molecular Sciences. 2020; 21(18):6852. https://doi.org/10.3390/ijms21186852
Chicago/Turabian StyleMasár, Marián, Jasna Hradski, Martin G. Schmid, and Roman Szucs. 2020. "Advantages and Pitfalls of Capillary Electrophoresis of Pharmaceutical Compounds and Their Enantiomers in Complex Samples: Comparison of Hydrodynamically Opened and Closed Systems" International Journal of Molecular Sciences 21, no. 18: 6852. https://doi.org/10.3390/ijms21186852
APA StyleMasár, M., Hradski, J., Schmid, M. G., & Szucs, R. (2020). Advantages and Pitfalls of Capillary Electrophoresis of Pharmaceutical Compounds and Their Enantiomers in Complex Samples: Comparison of Hydrodynamically Opened and Closed Systems. International Journal of Molecular Sciences, 21(18), 6852. https://doi.org/10.3390/ijms21186852