[Injectable hospital preparation of valine labeled with the carbon 13 and nitrogen 15 (5 mg/mL) for a clinical trial on the brain tumor metabolism: Pharmaceutical control of active pharmaceutical ingredient and stability study of the finished product]. / Préparation hospitalière injectable de valine marquée au carbone 13 et à l'azote 15 (5mg/mL) pour un essai clinique sur le métabolisme tumoral cérébral : contrôle pharmaceutique de la substance active et étude de stabilité du produit fini.

ABSTRACT

INTRODUCTION: The L-Valine labeled (L-[U-(13)C,(15)N] Val) is a stable isotopic tracer administered by parenteral route within the framework of a new clinical research program concerning the brain tumor metabolism. To meet regulatory requirements and have ready to use solution with an expiration date, a pharmaceutical control of active pharmaceutical ingredient followed by stability study of hospital preparation were realised. MATERIALS AND METHODS: After the pharmaceutical control of the L-[U-(13)C,(15)N] Val, the hospital preparation was prepared according to the good manufacturing preparation. Prepared bottles were stored at 5°C±3°C and 25°C±2°C for six months. The stability of the preparation was determined by physico-chemical controls (pH, osmolality, sub-visible particles, L-[U-(13)C,(15)N] Val concentration, sodium concentration, isotopic enrichment) and microbiological (bacterial endotoxin and sterility). RESULTS: Concentrations of L-[U-(13)C, (15)N] Val and sodium does not significantly decrease during the stability study. In parallel, no change in pH and osmolality were highlighted. Isotopic enrichment higher than 99.9% reflected the stability of labeling of L-valine 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 stability of this hospital preparation of L-[U-(13)C, (15)N] Val has been demonstrated for six months at 5°C±3°C and 25°C±2°C, ensuring a parenteral administration as part of the clinical trial.