Determination of the new anticancer agent KW 2149, 7-N-[2-[2-(gamma-L-glutamylamino)ethyl)dithio)ethyl]mitomycin C, an analogue of mitomycin C.
The new mitomycin 7-N-[2-[2-(gamma-L-glutamylamino)ethyl)dithio)ethyl] mitomycin C (KW 2149) (I) proved to be active against a wide variety of experimental tumours. In order to perform pharmacokinetic studies with the new drug in Phase I sessions, a fast and reliable method has been developed based on the data of previous assays for mitomycin C. XAD-2 was preferred for isolation of I from blood plasma. The recovery of I was 50% whereas that of mitomycin C was 85%. Optimal separation was obtained on octadecyl silica columns with methanol-water (45:55, v/v) as mobile phase, while ultraviolet absorbance detection was performed at 375 nm. The assay enabled determination of I in a plasma concentration range of 20-1000 ng/ml using porfiromycin as internal standard.
Pattyn
G
G
Laboratory of Cancer Research and Clinical Oncology, University of Antwerp, Wilrijk, Belgium.
van Oosterom
A T
AT
de Bruijn
E A
EA
Tjaden
U R
UR
D000970:Antineoplastic Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards; D006801:Humans; D008937:Mitomycins / Q000097:blood* / Q000737:chemistry; D015394:Molecular Structure; D011160:Porfiromycin
D000970:Antineoplastic Agents; D008937:Mitomycins; C057625:KW 2149; D011160:Porfiromycin