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Ann Pharm Fr. 2015 Jan;73(1):43-59. doi: 10.1016/j.pharma.2014.06.002. Epub 2014 Jul 11.

[Injectable preparation of labeled leucine with the carbon 13 for a clinical research program on the Alzheimer disease: pharmaceutical control of raw materials and the finished product and stability study].

[Article in French]

Author information

1
Service pharmaceutique, groupement hospitalier Édouard-Herriot, 5, place d'Arsonval, 69437 Lyon cedex 03, France. Electronic address: mamadou-lamine.tall@chu-lyon.fr.
2
Laboratoire de biochimie - protéomique clinique, hôpital St-Éloi, centre hospitalo universitaire de Montpellier, 80, avenue Augustin-Fliche, 34295 Montpellier, France.
3
Service pharmaceutique, groupement hospitalier Édouard-Herriot, 5, place d'Arsonval, 69437 Lyon cedex 03, France.
4
Centre de recherche en nutrition humaine, Rhône-Alpes & centre européen nutrition santé, groupement hospitalier Sud, 165, chemin du Grand-Revoyet, 69495 Pierre-Bénite cedex, France.
5
Service pharmaceutique, groupement hospitalier Édouard-Herriot, 5, place d'Arsonval, 69437 Lyon cedex 03, France; Laboratoire de recherche et développement de pharmacie galénique industrielle, faculté de pharmacie, EA 4169 « fonctions physiologiques et pathologiques de la barrière cutanée », université Claude-Bernard Lyon 1, 8, avenue Rockefeller, 69373 Lyon cedex 08, France.

Abstract

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

PMID:
25577016
DOI:
10.1016/j.pharma.2014.06.002
[Indexed for MEDLINE]

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