RT Journal Article
SR Electronic
T1 Pharmaceutical Quality Control of the Investigational Polymer-conjugated Platinum Anticancer Agent AP 5280
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP 198
OP 207
VO 57
IS 3
A1 Marjan Bouma
A1 Bastiaan Nuijen
A1 Donald R. Stewart
A1 Kevin F. Shannon
A1 John V. St. John
A1 John R. Rice
A1 Remko Harms
A1 Bart A.J. Jansen
A1 Steven van Zutphen
A1 Jan Reedijk
A1 Auke Bult
A1 Jos H. Beijnen
YR 2003
UL http://journal.pda.org/content/57/3/198.abstract
AB 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.