Validation study of assay method for DE-310, a novel polymer-bound camptothecin derivative, and the free drug in mouse plasma by liquid chromatography with fluorimetric detection.
DE-310 is a macromolecular carrier conjugate containing an anti-tumor camptothecin derivative, DX-8951, which is conjugated to a water-soluble polymer via a peptide spacer. Assay methods have been developed for the determination of a polymer-bonded DX-8951 conjugate, DX-8951, and Glycyl-DX-8951 (G-DX-8951) in mouse plasma. Free DX-8951 and Glycyl-DX-8951 were extracted from plasma by protein precipitation and analyzed by HPLC (Method I). Conjugated DX-8951 was extracted by protein precipitation and digested by using a thermolysin. The productive compound was analyzed by HPLC (Method II). The lower limits of quantitation of DX-8951, Glycyl-DX-8951, and Conjugated DX-8951 were 0.60, and 0.77 ng/ml and 3.45 microg/ml (as DX-8951 equivalent). These two methods showed satisfactory sensitivity, precision, accuracy, recovery, and selectivity.
Oguma
Toshihiro
T
Drug Metabolism and Physicochemical Property Research Laboratory, Daiichi Pharmaceutical Co. Ltd., 1-16-13 Kitakasai, Edogawa-ku, 134-8630 Tokyo, Japan. ogumab0g@daiichipharm.co.jp
Konno
Tomomi
T
Nakaoka
Minoru
M
D000818:Animals; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood*; D011232:Chemical Precipitation; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005470:Fluorometry; D051379:Mice; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013820:Thermolysin
C452060:DE-310 cpd; D013820:Thermolysin; D002166:Camptothecin