Introduction: The L-leucine labeled (L-[U-(13)C] 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-(13)C] 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-(13)C] Leu concentration, sodium concentration, isotopic enrichment) and microbiological (bacterial endotoxin and sterility) were performed at regular intervals for 1 year.
Results: Neither significant decrease of L-[U-(13)C] Leu concentration and sodium concentration nor pH and osmolality variation were observed for 1 year. 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-(13)C] Leu was stable after 1 year for two preservation conditions, ensuring to safety for administration for human within the framework of this clinical research.
Keywords: Alzheimer's disease; Clinical research; Contrôle pharmaceutique; Finished product; Isotope stable; L-leucine labelled; L-leucine marquée; Maladie d’Alzheimer; Matière première; Pharmaceutical control; Produit fini; Raw material; Recherche clinique; Stability; Stabilité; Stable isotope.
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