Abstract
Statins are the most prescribed HMG CoA reductase inhibitors for the treatment of anti-hyperlipidemia either alone or in combination with other pharmacotherapeutic agents. Nonetheless, adverse effects like rhabdomyolysis and myotoxicity had been reported in the literature on the long-term use of statins. Numerous clinical trials have been performed to learn the beneficial and adverse effects of combining statins with other pharmacotherapeutic agents. Being one of the most prescribed, statins have been frequently reported for their stability issues. We have reviewed the liquid and planar chromatographic methods coupled with UV and mass spectrometric detection systems (HPTLC, HPLC-UV, and LC-MS/MS) and tried to establish the effect of different stressor media on the stability of statins and the relation between different degradation pathways. Statins are highly susceptible to hydrolytic, oxidative, and photolytic degradation and frequently undergo chemical modifications like lactonization, hydrolysis, esterification, dimerization, and isomerization in different stressor media. The lactone form of statin has been reported to induce myotoxicity. However, structurally similar degradation products have been reported to be generated in acidic stressor media, while the primary degradation product of statins under oxidative and photolytic stress is epoxide impurity which has a structural alert for potential genotoxicity. The order for the stability of statins is acidic hydrolysis ≈ photolytic > oxidative hydrolysis > neutral > basic hydrolysis. On the contrary, Simvastatin has shown higher susceptibility towards basic hydrolysis than acidic ones. The relative determination of resultant degradation products of statins may be an alternative pathway to establish a link between adverse effects and stability of this pharmacotherapeutic class.
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Abbreviations
- ATR:
-
Atorvastatin
- RSV:
-
Rosuvastatin
- FLV:
-
Fluvastatin
- LOVA:
-
Lovastatin
- EZE:
-
Ezetimibe
- CLOPI:
-
Clopidogrel
- SIAM:
-
Stability indicating assay method
- RRT:
-
Relative Retention Time
- HILIC:
-
Hydrophilic interaction liquid chromatography method
- ODS:
-
Octadecyl-silica
- TEA:
-
Triethylamine
- TFA:
-
Trifluoroacetic acid
- THF:
-
Tetrahydrofuran
- PCSK9:
-
Proprotein convertase subtilisin-kexin type 9
- RS:
-
Related Substance
- QIT-MS:
-
Quadrupole ion trap-mass spectrometer
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Lalchandani, D.S., Chenkual, L., Mariappayan, M. et al. Significance of stressor media on the stability of statins: a critical assessment. Chem. Pap. 76, 6047–6071 (2022). https://doi.org/10.1007/s11696-022-02306-w
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DOI: https://doi.org/10.1007/s11696-022-02306-w