Preparation of intravenous cholesterol tracer using current good manufacturing practices.

Autor:	Lin X; Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO., Ma L; Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO., Racette SB; Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO Program in Physical Therapy, Washington University School of Medicine, St. Louis, MO., Swaney WP; Biologic Therapeutics Center, Washington University School of Medicine, St. Louis, MO., Ostlund RE Jr; Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO rostlund@dom.wustl.edu.
Jazyk:	angličtina
Zdroj:	Journal of lipid research [J Lipid Res] 2015 Dec; Vol. 56 (12), pp. 2393-8. Date of Electronic Publication: 2015 Sep 28.
DOI:	10.1194/jlr.D061762
Abstrakt:	Studies of human reverse cholesterol transport require intravenous infusion of cholesterol tracers. Because insoluble lipids may pose risk and because it is desirable to have consistent doses of defined composition available over many months, we investigated the manufacture of cholesterol tracer under current good manufacturing practice (CGMP) conditions appropriate for phase 1 investigation. Cholesterol tracer was prepared by sterile admixture of unlabeled cholesterol or cholesterol-d7 in ethanol with 20% Intralipid(®). The resulting material was filtered through a 1.2 micron particulate filter, stored at 4°C, and tested at time 0, 1.5, 3, 6, and 9 months for sterility, pyrogenicity, autoxidation, and particle size and aggregation. The limiting factor for stability was a rise in thiobarbituric acid-reacting substances of 9.6-fold over 9 months (P < 0.01). The emulsion was stable with the Z-average intensity-weighted mean droplet diameter remaining at 60 nm over 23 months. The zeta potential (a measure of negative surface charge protecting from aggregation) was unchanged at -36.2. Rapid cholesterol pool size was 25.3 ± 1.3 g. Intravenous cholesterol tracer was stable at 4°C for 9 months postproduction. CGMP manufacturing methods can be achieved in the academic setting and need to be considered for critical components of future metabolic studies. (Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.)
Databáze:	MEDLINE
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