Atorvastatin Forced Degradation by LC-MS - AppNote
May 1, 2012
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Date: 1-MAY-2012 Last Updated: 16-SEPTEMBER-2026
Separation of API from its Lactone Degradation Product
Atorvastatin is separated from its main Degradation product in this Method with a simple linear Reversed Phase Gradient. With the use of LCMS, the identity of the Degradant can be confirmed from its m/z value. The Degradation is an intramolecular Fischer esterification, which is catalyzed under Acidic conditions.
Figure A
shows the extracted Ion Chromatogram (EIC) corresponding to Atorvastatin for the Non-Degraded extract.
Figures B and C
show the EICs of Atorvastatin and the Lactone Degradant respectively for the Acid-Degraded extract.
Peaks: 1. Atorvastatin, 2. Atorvastatin Lactone
Method ConditionsColumn: Cogent Bidentate C18™, 4 µm, 100 Å
Catalog No.: 40018-05P-2
Dimensions: 2.1 x 50 mm
Mobile Phase:
-- A: 50% DI Water / 50% Methanol / 10 mM Ammonium Acetate
-- B: 90% Acetonitrile / 10% DI Water / 10 mM Ammonium Acetate
Gradient:
| Time (minutes) | %B |
|---|---|
| 0 | 30 |
| 10 | 100 |
| 12 | 30 |
Detection: ESI — POS - Agilent 6210 MSD TOF Mass Spectrometer
Sample Preparation:
-- Tablet Stock Solution: A 40mg strength tablet was ground and added to a 100mL volumetric flask. A 50mL portion of Solvent B was added to the flask. The solution was vortexed 5 minutes, sonicated 5 minutes, and diluted to mark with Solvent A. It was then filtered through a 0.45µm Nylon Syringe Filter (MICROSOLV Technology Corp.).
-- Degraded Tablet Stock Solution: A 40mg strength tablet was ground and added to a 100mL volumetric flask. A 50mL portion of Solvent B was added to the flask. It was then vortexed 5 minutes, sonicated 5 minutes, and diluted to mark with 3M HCl. It was then filtered through a 0.45µm Nylon Syringe Filter (MICROSOLV Technology Corp.).
-- Fig. A: 10µL tablet stock diluted with 990µL 50:50 A:B
-- Fig. B and C: 10µL degraded tablet stock diluted with 990µL 50:50 A:B
Note: Atorvastatin is a competitive inhibitor of 3-Hydroxy-3-Methlyglutaryl Coenzyme A (HMG- CoA) Reductase, which Catalyzes the rate limiting step in Cholesterol Biosynthesis. As such, Atorvastatin is used to reduce plasma levels of low-density Lipoprotein (LDL) Cholesterol, which are known to contribute to the development of Atherosclerosis. Atorvastatin is marketed by Pfizer under the trade name Lipitor.
