[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].
BACKGROUND
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.


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.


CONCLUSIONS
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.
Pharmacie, groupement hospitalier Édouard-Herriot, plateforme Fripharm, 5, place d'Arsonval, 69437 Lyon cedex 03, France. Electronic address: mamadou-lamine.tall@chu-lyon.fr.
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Tall
Pharmacie, groupement hospitalier Édouard-Herriot, plateforme Fripharm, 5, place d'Arsonval, 69437 Lyon cedex 03, France.
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Diouf
Pharmacie, groupement hospitalier Édouard-Herriot, plateforme Fripharm, 5, place d'Arsonval, 69437 Lyon cedex 03, France.
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Filali
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.
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Sauvinet
Pharmacie, groupement hospitalier Édouard-Herriot, plateforme Fripharm, 5, place d'Arsonval, 69437 Lyon cedex 03, France.
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Laleye
Pharmacie, groupement hospitalier Édouard-Herriot, plateforme Fripharm, 5, place d'Arsonval, 69437 Lyon cedex 03, France.
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Dhelens
Pharmacie, groupement hospitalier Édouard-Herriot, plateforme Fripharm, 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.
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Salmon
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.
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Gabert
Centre de recherche biomédicale Edmond-J.-Safra, 17, rue des Martyrs, 38054 Grenoble cedex 9, France; Institut de recherche biomédicale des armées, BP 73, 91223 Brétigny/Orge cedex, France.
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Nugue
Centre de recherche biomédicale Edmond-J.-Safra, 17, rue des Martyrs, 38054 Grenoble cedex 9, France; Centre hospitalier universitaire de Grenoble, CS 10217, 38043 Grenoble cedex 9, France.
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Sandre-Balester
Centre de recherche biomédicale Edmond-J.-Safra, 17, rue des Martyrs, 38054 Grenoble cedex 9, France; Centre hospitalier universitaire de Grenoble, CS 10217, 38043 Grenoble cedex 9, France.
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Berger
Pharmacie, groupement hospitalier Édouard-Herriot, plateforme Fripharm, 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.
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Pirot
Pharmacie, groupement hospitalier Édouard-Herriot, plateforme Fripharm, 5, place d'Arsonval, 69437 Lyon cedex 03, France.
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Pivot
D001932:Brain Neoplasms / Q000378:metabolism*; D002247:Carbon Isotopes; D004339:Drug Compounding; D004355:Drug Stability; D007267:Injections; D007553:Isotope Labeling; D009587:Nitrogen Isotopes; D019999:Pharmaceutical Solutions; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D014633:Valine / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*
D002247:Carbon Isotopes; D009587:Nitrogen Isotopes; D019999:Pharmaceutical Solutions; D019275:Radiopharmaceuticals; D014633:Valine
Active pharmaceutical ingredient; Brain tumor; Clinical research; Contrôle pharmaceutique; Finished product; Glioblastome; Hospital preparation; Isotope stable; L-valine labeled; L-valine marquée; Métabolisme tumoral; Pharmaceutical control; Produit fini; Préparation hospitalière; Recherche clinique; Stability; Stabilité; Stable isotope; Substance active