Bioequivalence and Bioavailability Forum

Dear Ioanam,

Back-conversion of clopidogrel metabolites is known, but still not fully understood and explained. Is is indeed known that methanol (during the sample extraction, or in the mobile phase) can cause this back-conversion, but other factors may be involved too. I think there were also reports of back-conversion in the absence of methanol, when using some specific solid phase extraction columns.

In fact it is not even sure which metabolite is back converted. It was initially said to be clopidogrel carboxyacid, but a poster at ASMS 2010 says it is due to transesterification of clopidogrel acyl glucuronide.

Fabio Garofolo and colleagues from Algorithme Pharma made several communications and posters on clopidogrel and back-conversion. Have a look on Internet.

Regarding your current study what I would suggest if you have enough sample volume would be to try incurred sample re-analysis. If you see wide differences between your first and second result you'll be quite sure you have a back-conversion problem.