Multivariate Chemometric Comparison of Forced Degradation and Electrochemical Oxidation LC–MS Profiles of Maraviroc
Abstract
:1. Introduction
2. Results and Discussion
2.1. Optimization of the LC–ESI–MS/MS and EC Methods
2.2. Chemometric Study
2.3. Identification of Forced Degradation Products
2.4. Degradation Pathway
3. Materials and Methods
3.1. Chemicals and Reagents
3.2. Forced Degradation Studies
3.3. Electrochemical Studies
3.4. LC–ESI–MS/MS Analysis
3.5. Data Preprocessing and Chemometric Studies
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Name | Observed in Stress Condition | Retention Time [min] | Mass [m/z] | Mass Error [ppm] | Molecular Formula [M+H]+ | Fragmentation MS/MS | ||
---|---|---|---|---|---|---|---|---|
Measured | Theoretical | Mass [m/z] | Ion Formula [M+H]+ | |||||
Maraviroc | 4.25 | 514.3349 | 514.3352 | 0.58 | C29H42F2N5O | 389.2397 280.1512 260.1438 235.1878 226.1587 205.1428 185.1227 * 144.0816 124.1026 117.0703 106.0656 99.0604 91.0540 79.0554 | C23H31F2N2O C16H20F2NO C16H19FNO C13H23N4 C16H20N C11H17N4 C22H35N5* C7H11FNO C8H14N C9H9 C7H8N C6H8F C7H7 C6H7 | |
TP1 | UVA, Pt, GC | 0.7 | 235.1921 | 235.1917 | 1.70 | C13H23N4 | 207.1849 126.1023 110.0971 93.0697 82.0651 67.0551 | C13H23N2 C6H12N3 C7H12N C7H9 C5H8N C5H7 |
TP2 | NaOH | 1.04 | 368.2793 | 368.2809 | 4.34 | C22H34N5 | 243.1893 124.1122 96.0823 70.0672 | C16H23N2 C8H14N C6H10N C4H8N |
TP3 | UVA | 3.54 | 530.3306 | 530.3301 | 0.94 | C29H42F2N5O2 | 405.2332 296.1450 247.1923 242.1535 205.1470 164.0888 144.0816 133.0620 124.1105 99.0612 | C23H31F2N2O2 C16H20F2NO2 C14H23N4 C16H20NO C11H17N4 C7H12F2NO C7H11FNO C9H9O C8H14N C6H8F |
TP4 | UVA | 3.71 | 530.3306 | 530.3301 | 0.94 | C29H42F2N5O2 | 405.2352 296.1451 247.1933 205.1456 144.0830 133.0641 124.1134 122.0589 119.0672 110.0971 99.0631 | C23H31F2N2O2 C16H20F2NO2 C14H23N4 C11H17N4 C7H11FNO C9H9O C8H14N C7H8NO C6H9F2 C7H12N C6H8F |
TP5 | UVA | 4.12 | 530.3306 | 530.3301 | 0.94 | C29H42F2N5O2 | 405.2355 296.1468 247.1897 242.1514 144.0831 133.0638 124.1123 122.0962 119.0652 110.0971 99.0653 | C23H31F2N2O2 C16H20F2NO2 C14H23N4 C16H20NO C7H11FNO C9H9O C8H14N C8H12N C6H9F2 C7H12N C6H8F |
TP6 | UVA, H2O2, Au, Pt | 4.25 | 530.3285 | 530.3301 | 3.02 | C29H42F2N5O2 | 389.2387 280.1512 251.1860 144.0851 126.0948 117.0693 106.0652 99.0629 91.0536 | C23H31F2N2O C16H20F2NO C13H22N4O C7H11FNO C7H11NO C9H9 C7H8N C6H8F C7H7 |
TP7 | UVA, H2O2, Au, Pt | 4.43 | 530.3312 | 530.3301 | 2.07 | C29H42F2N5O2 | 405.2344 280.1508 251.1867 184.1311 * 144.0810 126.0933 117.0701 106.0656 99.0656 81.0707 67.0536 | C23H31F2N2O2 C16H20F2NO C13H22N4O C22H32N4O* C7H11FNO C7H12NO C9H9 C7H8N C6H8F C6H9 C5H7 |
TP8 | UVA | 4.49 | 546.3284 | 546.3250 | 6.22 | C29H42F2N5O3 | 514.2988 389.2441 280.1550 243.1861 185.1193 * 144.0821 140.0940 * 124.1092 119.0640 | C29H42F2N5O C23H31F2N2O C16H20F2NO C16H23N2 C22H34N4O * C7H11FNO C14H24N4O2* C8H14N C6H9F2 |
TP9 | GC, Au | 5.7 | 528.3137 | 528.3145 | 1.51 | C29H40F2N5O2 | 294.1297 252.1195 240.1364 148.0765 131.0492 126.1029 119.0666 110.0966 106.0653 99.0611 93.0703 79.0543 67.0554 | C16H18F2NO2 C14H16F2NO C16H18NO C9H10O C9H7O C6H12N3 C6H9F2 C7H12N C7H8N C6H8F C7H9 C6H7 C5H7 |
Stress Conditions | Diluting Solvent | Exposure Conditions | Duration (h) |
---|---|---|---|
Acid hydrolysis | 0.2 M HCl | 80 °C | 3 |
Alkaline hydrolysis | 0.2 M NaOH | 80 °C | 3 |
Neutral hydrolysis | H2O | 80 °C | 3 |
Oxidation | 1% H2O2 | Room temperature | 3 |
Photolysis (UVA) | H2O | Room temperature | 1 |
Device | Parameter | Value |
---|---|---|
LC | Solvents | A—0.1% aqueous solution of HCOOH B—acetonitrile |
Gradient | 10% B to 55% B | |
Analysis time | 8 min | |
Post-time equilibration | 2 min | |
Flow rate | 0.3 mL min−1 | |
Injection volume | 1.5 µL | |
Column temperature | 40 °C | |
MS | Ion source | Electrospray (ESI) |
Mode | Positive | |
Source temperature | 325 °C | |
Drying gas flow | 10 L min−1 | |
Nebulizer pressure | 40 psig | |
Capillary voltage | 3500 V | |
Fragmentor voltage | 150 V | |
Skimmer voltage | 65 V | |
Octopole voltage | 750 V | |
Mass range | 60–1050 m/z | |
Acquisition rate | 2 spectra s−1 * |
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Wroński, M.; Trawiński, J.; Komsta, Ł.; Skibiński, R. Multivariate Chemometric Comparison of Forced Degradation and Electrochemical Oxidation LC–MS Profiles of Maraviroc. Molecules 2023, 28, 1195. https://doi.org/10.3390/molecules28031195
Wroński M, Trawiński J, Komsta Ł, Skibiński R. Multivariate Chemometric Comparison of Forced Degradation and Electrochemical Oxidation LC–MS Profiles of Maraviroc. Molecules. 2023; 28(3):1195. https://doi.org/10.3390/molecules28031195
Chicago/Turabian StyleWroński, Michał, Jakub Trawiński, Łukasz Komsta, and Robert Skibiński. 2023. "Multivariate Chemometric Comparison of Forced Degradation and Electrochemical Oxidation LC–MS Profiles of Maraviroc" Molecules 28, no. 3: 1195. https://doi.org/10.3390/molecules28031195