Préparation injectable de leucine marquée au carbone 13pour un programme de recherche clinique sur la maladie d'Alzheimer: Contrôle pharmaceutique des matières premières et du produit fini et étude de stabilitthomamper

Abstract

Introduction: The L-leucine labeled (L-[U-13C] Leu) is a stable isotopic tracer administered by parenteral route within the framework of a new clinical research program concerning the diagnosis of the Alzheimer's disease. To meet regulatory requirements and have ready to use solution with an expiration date, a pharmaceutical control of raw materials and the finished product followed by a stability study were realised. Materials and method: After the pharmaceutical control of raw materials, the solution of L-[U-13C] Leu was prepared according to the good practices preparation. Prepared bottles were stored for 1 year of a share in a climatic chamber (25°C±2°C) and the other in a refrigerator (5°C±3°C). To assess stability, the physicochemical controls (pH, osmolality, sub-visible particles, L-[U-13C] Leu concentration, sodium concentration, isotopic enrichment) and microbiological (bacterial endotoxin and sterility) were performed at regular intervals for 1year. Results: Neither significant decrease of L-[U-13C] Leu concentration and sodium concentration nor pH and osmolality variation were observed for 1year. Isotopic enrichment higher than 99.9% reflected the stability of labelling of L-leucine molecule. The sub-visible particles, the bacterial endotoxin and sterility were in accordance with the European pharmacopoeia attesting limpidity, apyrogenicity and sterility of this injectable preparation. Discussion and conclusion: The injectable preparation of L-[U-13C] Leu was stable after 1year for two preservation conditions, ensuring to safety for administration for human within the framework of this clinical research.