Analysis of the API and Degradants

A Sensitive, Selective, and rapid LCMS Method was developed for the simultaneous Quantification of Clopidogrel (Plavix®) and degradants.

This Method can be used for the determination of Clopidogrel in commercial tablets for Quality Control with an application for content uniformity test. The Method is also stability-indicating as it is suitable for the determination of the API in the presence of its degradation products under all stress conditions using HCL, NaOH, light and Hydrogen Peroxide.

1. API: Clopidogrel, m/z 322.0663 [M+H]+
2. Degradant: Clopidogrel Acid, m/z 308.0507 [M+H]+
3. Degradant: Clopidogrel N-oxide, m/z 338.02 [M+H]+

Method Conditions
Column: Cogent Diamond Hydride™, 4μm, 100Å
Catalog No.: 70000-15P-2
Dimensions: 2.1 x 150mm
Mobile Phase:
A: DI Water / 0.1% Formic Acid (v/v)
B: Acetonitrile / 0.1% Formic Acid (v/v)

Time (minutes) %B
0 95
2 95
7 60
8 95

Temperature: 25˚C
Post Time: 3 minutes
Injection vol.: 1μL
Flow rate: 0.4mL / minute
Detection: ESI – POS – Agilent 6210 MSD TOF Mass Spectrometer
Sample Preparation: 50mg strength Plavix® tablet was ground and diluted in 50:50 Solvent A / Solvent B mixture to 50mL. The solution was sonicated and filtered through a 0.45μm Nylon Syringe Filter (MicroSolv Tech Corp.).
t0: 0.9 minutes

Fig. 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.
Fig. B: 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 minutes. The API peak is no longer observed but degradants (Peak 2 and 3) are now present.


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