Photochemical activity of glenvastatin, a HMG-CoA reductase inhibitor

Photochemical properties of glenvastatin (HR 780), a HMG-CoA reductase inhibitor, were studied. The drug was exposed to light in liquid state under aerobic conditions. The source of irradiation was an HBO-50 lamp. The lamp was equipped with a mercury burner and an appropriate set of glass filters. The conditions during photodegradation were the same as specified in the first version of the ICH Document.Photoproducts formed after illumination of a methanol solution of glenvastatin were identified by several analytical techniques, including: spectrophotometry, HPLC and HPLC–MS. Quantitative evaluation of photochemical degradation of glenvastatin was made on the basis of UV–Vis spectrophotometric and HPLC. The irradiation photodecomposition of glenvastatin led preferentially to two main photoproducts being stereoisomers. The photoproducts were isolated with the help of a semipreparative HPLC method and identified by mass spectrometry. As a result of glenvastatin exposure to irradiation, the heptene chain is oxidised and its cyclisation takes place with formation of two diastereoisomers containing three condensed rings.

Glenvastatin exposure to irradiation, the heptene chain is oxidised and its cyclisation takes place with formation of two diastereoisomers containing three condensed rings.Figure optionsDownload as PowerPoint slideHighlights
► Glenvastatin – a HMG-CoA reductase inhibitor – is very sensitivity to light.
► Photoproducts were identified by spectrophotometry, HPLC and HPLC–MS.
► The products of photochemical decomposition of glenvastatin are diastereoisomers.