title: Studies on the stability of vinblastine sulfate in aqueous solution.
abstract: A stability study on vinblastine sulfate (1) in aqueous solution at several different temperatures (in the absence of light) has been undertaken. High-performance liquid chromatography was used to obtain kinetic data for the loss of vinblastine and to monitor the order of appearance of degradation products, of which eight were observed. The two most prominent components of early heat degradation have been tentatively identified by mass spectrometry (DCl), as a C19'-oxidation product (19'-oxovinblastine, 4, MH+ 825) and an isomer of vinblastine (MH+ 811). Products appearing later in the course of degradation include a component of MH+ 809, possibly corresponding to either 19'-hydroxy-3',4'-dehydrovinblastine (5) or 3',4'-dehydrovinblastine-6'-N-oxide (6), and three other products of MH+ 636, MH+ 670, and MH+ 795. In addition, optical rotation studies have established that racemization (with a possible reduction in biological activity) does not occur prior to transformation into degradation products. Preliminary experiments on light-mediated degradation demonstrated a different sequence of transformation, with the MH+ 670 and MH+ 795 products appearing first. Contrary to reports and suggestions in the literature and based on an estimated activation energy of 27.1 kcal/mol, the results of this study indicate that vinblastine sulfate is relatively stable in aqueous solution at or below room temperature (estimated t90 values: 150 d at 25 degrees C and 10.7 years at 5 degrees C) and has a t90 value of 16.6 d at 37 degrees C. These results are important in view of current interest in the continuous iv infusion of vinblastine sulfate.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Medicinal Chemistry, College of Pharmacy, University of Texas, Austin 78712.
authors.forename: J
authors.initials: J
authors.lastname: Black
authors.forename: D D
authors.initials: DD
authors.lastname: Buechter
authors.forename: J W
authors.initials: JW
authors.lastname: Chinn
authors.forename: J
authors.initials: J
authors.lastname: Gard
authors.forename: D E
authors.initials: DE
authors.lastname: Thurston
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D013058:Mass Spectrometry; D012996:Solutions; D013696:Temperature; D013997:Time Factors; D014747:Vinblastine / Q000032:analysis*
chemical_list: D012996:Solutions; D014747:Vinblastine