A stability-indicating assay and the preformulation characteristics of the radiosensitizer, 1,2,4-benzotriazin-3-amine 1,4-dioxide.
A stability-indicating LC assay was developed for the analysis of 1,2,4-benzotriazin-3-amine 1,4-dioxide and applied to the preformulation characterization of the drug. The dissociation constants of the drug were determined using UV-vis spectrophotometry. The LC method was used to determine the aqueous stability of the drug under a variety of accelerated conditions, its solubility in a variety of pharmaceutical solvents and its octan-1-ol-water partition coefficient. The preformulation data were used to develop three prototype aqueous formulations of the drug at a concentration of 0.5 mg ml-1 in 5% Dextrose Injection USP, phosphate buffer (pH 7.4) and phosphate buffered mannitol. The 3-month stability of those formulations at room temperature was demonstrated.
Riley
C M
CM
Center for BioAnalytical Research, University of Kansas, Lawrence 66045.
Shetty
B V
BV
Chetwyn
N C
NC
Kasper
V T
VT
Kindberg
C G
CG
Dicken
C M
CM
D002021:Buffers; D002853:Chromatography, Liquid; D004355:Drug Stability; D006868:Hydrolysis; D011838:Radiation-Sensitizing Agents / Q000737:chemistry*; D015203:Reproducibility of Results; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature; D000077704:Tirapazamine; D014227:Triazines / Q000737:chemistry*; D014867:Water
D002021:Buffers; D011838:Radiation-Sensitizing Agents; D014227:Triazines; D014867:Water; D000077704:Tirapazamine