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Forced Degradation of Clopidogrel
LC-MS Compatible Separation of API from Degradants
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printable Application Sheet
Figures:
A: Non-degraded extract: The stock solution was diluted 1:10 with 50/50 solvent A/solvent B mixture. Only the API peak is observed.
B: Base degradation: The stock solution was diluted 1:10 with 50/50 1N NaOH/Acetonitrile mixture. Two degradants are now present.
C: Base degradation with heating: The stock solution was diluted 1:10 with 50/50 1N NaOH/Acetonitrile mixture and then heated at 85°C for 30 min. The API peak is no longer observed but a third degradant (Peak 1) is now present.
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Method Conditions
| Column |
Cogent Diamond Hydride™, 4µm, 100A |
| Catalog No. |
70000-7.5P |
| Dimensions |
4.6 x 75 mm |
| Mobile Phase |
| A: | DI H2O/ 0.1% (v/V) formic acid |
| B: | 95% Acetonitrile/ 0.1% (v/V) formic acid |
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| Gradient |
| time (min.) |
%B |
time (min.) |
%B |
| 0 |
95 |
7 |
60 |
| 2 |
95 |
8 |
95 |
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| Post Time |
2 min |
| Injection Vol. |
1 microL |
| Flow rate |
1.0 mL/min. |
| Detection |
UV 225 nm |
| Samples |
Stock Solution: 50 mg strength Plavix® tablet was ground and diluted in 50/50 solvent A/solvent B mixture to 50 mL. The
solution was sonicated and filtered through a 0.45 µm nylon syringe filter (MicroSolv Tech Corp). |
| Peaks |
1. Degradant
2. Clopidogrel (API)
3. Degradant
4. Degradant |
| t0 |
0.9 min |
Discussion
Although clopidogrel, commonly known as Plavix®, retains well in reverse phase, its degradants showed low retention even at high water
content. Therefore a method using the Diamond Hydride™ column was used in which the compounds are retained on the basis of polarity. This
method uses MScompatible solvents and provides excellent retention and separation between the API and three observed degradants.
Clopidogrel is a widely prescribed antiplatelet agent used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and
cerebrovascular disease. The U.S. patent for Plavix® is set to expire in May 2012.
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