Pharmaceutical quality control of the investigational polymer-conjugated platinum anticancer agent AP 5280.
AP 5280 is a novel polymer-conjugated platinum anticancer agent currently in Phase I clinical trials. In order to guarantee the quality of AP 5280 drug substance for use in the manufacture of a drug product for intravenous human use, an array of tests was utilized for its quality control. Proton nuclear magnetic resonance (1H NMR) spectroscopy and infrared (IR) spectroscopy were employed for structural identification. The molecular weight (MW) and MW distribution, which play a large role in the distribution of AP 5280 in vivo, were determined by Size Exclusion Chromatography (SEC). Platinum binding assessment was performed using platinum nuclear magnetic resonance (195Pt NMR) spectroscopy. The free platinum content and release profile of small platinum species, measured using Flameless Atomic Absorption Spectroscopy (F-AAS), were determined as a measure of molecular integrity, a very important aspect of its assumed mechanism of action. The total platinum content of the copolymer was determined employing flame Atomic Absorption Spectroscopy (AAS). The combined results of the analyses performed on AP 5280 drug substance provided a meaningful picture of its structure, size, and integrity--an excellent basis for its quality control.
Bouma
Marjan
M
Slotervaart Hospital/The Netherlands Cancer Institute, Department of Pharmacy & Pharmacology, 1066 EC Amsterdam, The Netherlands. M.Bouma@wza.nl
Nuijen
Bastiaan
B
Stewart
Donald R
DR
Shannon
Kevin F
KF
St John
John V
JV
Rice
John R
JR
Harms
Remko
R
Jansen
Bart A J
BA
van Zutphen
Steven
S
Reedijk
Jan
J
Bult
Auke
A
Beijnen
Jos H
JH
D000178:Acrylamides / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009944:Organoplatinum Compounds / Q000737:chemistry*; D011786:Quality Control; D013055:Spectrophotometry, Infrared; D013678:Technology, Pharmaceutical
D000178:Acrylamides; C438846:HPMA copolymer-platinate; D009944:Organoplatinum Compounds