Fractionation and characterization of a conjugate between a polymeric drug-carrier and the antitumor drug camptothecin

A conjugate between the antitumor drug camptothecin and the polymeric drug-carrier poly[N-(2-hydroxypropyl)methacrylamide] was synthesized and fractionated. The conjugate samples, both fractionated and unfractionated, were characterized with a multi-detector SEC system using three on-line detectors: a multi-angle light scattering photometer, a viscometer, and a refractometer. The used mobile phase (DMF + 0.01 M LiBr + 0.05 M CH3COOH) derives from previous experience with similar conjugates. Narrow molar mass distribution fractions of the conjugate obtained by means of a semipreparative LC system were used to derive the coefficients of the Mark-Houwink-Sakurada relationship and to check the universal calibration of the SEC system. This study has demonstrated that the conjugate elutes according to the hydrodynamic volume. Thus, a conventional SEC method that uses only an on-line refractometer detector, commercially available narrow standards, and the universal calibration is adequate for the characterization of the molar mass distribution. Also the size and the conformation of the conjugate were studied by means of the gyration radius-molar mass power law.