Characterization of two new degradation products of atorvastatin-calcium formed upon treatment with strong acids

  1. Jürgen Krauß,
  2. Monika Klimt,
  3. Markus Luber,
  4. Peter Mayer and
  5. Franz Bracher ORCID Logo

Submitting author affiliation: Ludwig-Maximilians-Universität München, München, Germany

Beilstein Arch. 2019, 201931. doi:10.3762/bxiv.2019.31.v1

Published 28 May 2019

  • Preprint

Abstract

Atorvastatin-calcium (Lipitor®, Sortis®) is a well-established cholesterol synthesis enzyme (CSE) inhibitor commonly used in the therapy of hypercholesterolemia. This drug is known to be sensitive to acid treatment, but only little data has been published on the structures of the degradation products. Here we report on to the identification of two novel degradation products of atorvastatin, which are formed only under drastic acidic conditions. While treatment with conc. sulfuric acid lead to a loss of the carboxanilide residue (accompanied by an expectable lactonization/dehydration process in the side chain), treatment with conc. aqueous hydrochloric acid gave a complex, bridged molecule under, C,C-bond formation of the lactone moiety with the pyrrole, migration of the isopropyl group and loss of the carboxanilide residue. The novel degradation products were characterized by NMR spectroscopy, HR-MS data and X-ray crystal structure analysis.

Keywords: Atorvastatin, stress test, degradation products, crystal structure, fragmentation, cyclization

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Krauß, J.; Klimt, M.; Luber, M.; Mayer, P.; Bracher, F. Beilstein Arch. 2019, 201931. doi:10.3762/bxiv.2019.31.v1

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