Stability of compounded thioguanine oral suspensions. 2011

Hamidreza Montazeri Aliabadi, and Marcel Romanick, and Vishwa Somayaji, and Parvin Mahdipoor, and Afsaneh Lavasanifar
University of Alberta (UA), Edmonton, Alberta, Canada.

PURPOSE. Updated information on the stability of compounded thioguanine oral suspensions prepared with currently available ingredients, as well as results of testing to determine if the addition of an antioxidant could extend shelf life by inhibiting formation of guanine, are presented. METHODS. Using triturated thioguanine tablets, three compounded suspensions were prepared: (1) a reference formulation containing methylcellulose and simple syrup, (2) an equivalent formulation using Ora-Plus and Ora-Sweet, and (3) an antioxidant-containing formulation prepared by adding ascorbic acid to the equivalent formulation. The compounded batches were stored at room temperature (19-23 °C). The chemical stability of the suspensions was evaluated immediately after compounding and at weekly intervals by a validated liquid chromatography-mass spectrometry (LCMS) assay method; physical stability was evaluated by regular visual checks and weekly pH testing. RESULTS. As demonstrated by serial LCMS testing, mean thioguanine levels in sampled batches of all three suspensions remained above accepted standards and mean guanine formation remained within acceptable limits for up to 63 days. The addition of ascorbic acid appeared to slow guanine formation but did not significantly extend the shelf life of the suspension. CONCLUSION. Compounded oral suspensions of thioguanine 20 mg/mL exhibited acceptable chemical and physical stability for up to nine weeks at 19-23 °C. The addition of ascorbic acid at a concentration of 0.1% to the suspension was not effective in consistently increasing the shelf life of the thioguanine suspensions.

UI MeSH Term Description Entries
D002853 Chromatography, Liquid Chromatographic techniques in which the mobile phase is a liquid. Liquid Chromatography
D004339 Drug Compounding The preparation, mixing, and assembly of a drug. (From Remington, The Science and Practice of Pharmacy, 19th ed, p1814). Drug Formulation,Drug Preparation,Drug Microencapsulation,Pharmaceutical Formulation,Compounding, Drug,Formulation, Drug,Formulation, Pharmaceutical,Microencapsulation, Drug,Preparation, Drug
D004355 Drug Stability The chemical and physical integrity of a pharmaceutical product. Drug Shelf Life,Drugs Shelf Lives,Shelf Life, Drugs,Drug Stabilities,Drugs Shelf Life,Drugs Shelf Live,Life, Drugs Shelf,Shelf Life, Drug,Shelf Live, Drugs,Shelf Lives, Drugs
D004356 Drug Storage The process of keeping pharmaceutical products in an appropriate location. Drug Storages,Storage, Drug,Storages, Drug
D006147 Guanine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000964 Antimetabolites, Antineoplastic Antimetabolites that are useful in cancer chemotherapy. Antineoplastic Antimetabolites
D000975 Antioxidants Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues. Anti-Oxidant,Antioxidant,Antioxidant Activity,Endogenous Antioxidant,Endogenous Antioxidants,Anti-Oxidant Effect,Anti-Oxidant Effects,Anti-Oxidants,Antioxidant Effect,Antioxidant Effects,Activity, Antioxidant,Anti Oxidant,Anti Oxidant Effect,Anti Oxidant Effects,Anti Oxidants,Antioxidant, Endogenous,Antioxidants, Endogenous
D013535 Suspensions Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (AEROSOLS) and other colloidal systems; water-insoluble drugs may be given as suspensions. Suspension
D013866 Thioguanine An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia. 6-Thioguanine,2-Amino-6-Purinethiol,Lanvis,Tabloid,Thioguanin-GSK,Thioguanine Anhydrous,Thioguanine Hemihydrate,Thioguanine Monosodium Salt,Thioguanine Tabloid,Tioguanina Wellcome,Tioguanine,2 Amino 6 Purinethiol,6 Thioguanine,Anhydrous, Thioguanine,Thioguanin GSK,ThioguaninGSK

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