title: [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].
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Service pharmaceutique, groupement hospitalier Édouard-Herriot, 5, place d'Arsonval, 69437 Lyon cedex 03, France. Electronic address: mamadou-lamine.tall@chu-lyon.fr.
authors.forename: M L
authors.initials: ML
authors.lastname: Tall
authors.affiliation: Laboratoire de biochimie - protéomique clinique, hôpital St-Éloi, centre hospitalo universitaire de Montpellier, 80, avenue Augustin-Fliche, 34295 Montpellier, France.
authors.forename: S
authors.initials: S
authors.lastname: Lehmann
authors.affiliation: Service pharmaceutique, groupement hospitalier Édouard-Herriot, 5, place d'Arsonval, 69437 Lyon cedex 03, France.
authors.forename: E
authors.initials: E
authors.lastname: Diouf
authors.affiliation: Service pharmaceutique, groupement hospitalier Édouard-Herriot, 5, place d'Arsonval, 69437 Lyon cedex 03, France.
authors.forename: C
authors.initials: C
authors.lastname: Gérard
authors.affiliation: Service pharmaceutique, groupement hospitalier Édouard-Herriot, 5, place d'Arsonval, 69437 Lyon cedex 03, France.
authors.forename: S
authors.initials: S
authors.lastname: Filali
authors.affiliation: Laboratoire de biochimie - protéomique clinique, hôpital St-Éloi, centre hospitalo universitaire de Montpellier, 80, avenue Augustin-Fliche, 34295 Montpellier, France.
authors.forename: A
authors.initials: A
authors.lastname: Gabelle
authors.affiliation: Laboratoire de biochimie - protéomique clinique, hôpital St-Éloi, centre hospitalo universitaire de Montpellier, 80, avenue Augustin-Fliche, 34295 Montpellier, France.
authors.forename: C
authors.initials: C
authors.lastname: Hirtz
authors.affiliation: 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.
authors.forename: L
authors.initials: L
authors.lastname: Gabert
authors.affiliation: 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.
authors.forename: V
authors.initials: V
authors.lastname: Sauvinet
authors.affiliation: 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.
authors.forename: F
authors.initials: F
authors.lastname: Pirot
authors.affiliation: Service pharmaceutique, groupement hospitalier Édouard-Herriot, 5, place d'Arsonval, 69437 Lyon cedex 03, France.
authors.forename: C
authors.initials: C
authors.lastname: Pivot
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D002247:Carbon Isotopes; D004355:Drug Stability; D004356:Drug Storage; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D007930:Leucine / Q000737:chemistry*; D019999:Pharmaceutical Solutions; D019275:Radiopharmaceuticals / Q000737:chemistry*
chemical_list: D002247:Carbon Isotopes; D019999:Pharmaceutical Solutions; D019275:Radiopharmaceuticals; D007930:Leucine
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