HPLC methods for the determination of bound and free doxorubicin, and of bound and free galactosamine, in methacrylamide polymer-drug conjugates

被引：28

作者：

Configliacchi, E ^{[1
]}

Razzano, G ^{[1
]}

Rizzo, V ^{[1
]}

Vigevani, A ^{[1
]}

机构：

[1] PHARMACIA,PHARMACEUT RES & DEV,I-20014 NERVIANO,ITALY

来源：

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS | 1996年 / 15卷 / 01期

关键词：

acid hydrolysis; doxorubicin; D-galactosamine; liver targetting; polymer-drug conjugates;

D O I：

10.1016/0731-7085(96)01825-0

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

Quantitative acid hydrolysis followed by HPLC separation has been established as an analytical procedure for the determination of polymer-bound doxorubicin (an anti-cancer drug) and D-galactosamine (a liver-targetting moiety) in the polymer-drug conjugates FCE 28068 and FCE 28069. Optimal conditions of hydrolysis were determined in both cases: 1 N HCl, 50 degrees C, 1.5 h for doxorubicin, and 6 N HCl, 60 degrees C, 5 h for galactosamine. Appropriate HPLC quantitation of galactosamine required pre-treatment with sodium borohydride and pre-column derivatization with o-phthalalaldehyde and beta-mercaptoethanol. Independent determination of free doxorubicin and glactosamine in untreated polymer samples was also achieved with the same HPLC method up to detection limits of 0.01% and 0.02% respectively. The methods were validated for linearity, precision and repeatability. Validation for accuracy before and after acid hydrolysis was achieved by testing hydrolysis on model compounds and by assessing recovery in polymer solutions spiked with free doxorubicin or galactosamine.

引用

页码：123 / 129

页数：7

共 7 条

[1]

ARCAMONE F, 1981, DOXORUBICIN, P20

[2]

BIERMNAN CJ, 1989, ANAL CARBOHYDRATES G

[3] DRUG POLYMER CONJUGATES - POTENTIAL FOR IMPROVED CHEMOTHERAPY [J].

DUNCAN, R .

ANTI-CANCER DRUGS, 1992, 3 (03) :175-210

[4]

DUNCAN R, 1984, MAKROMOL CHEM, V184, P1997

[5] Targeting of N-(2-Hydroxypropyl)Methacrylamide Copolymer-Doxorubicin Conjugate to the Hepatocyte Galactose-Receptor in Mice: Visualisation and Quantification by Gamma Scintigraphy as a Basis for Clinical Targeting Studies [J].

Pimm, M. V. ;

Perkins, A. C. ;

Duncan, R. ;

Ulbrich, K. .

JOURNAL OF DRUG TARGETING, 1993, 1 (02) :125-131

[6] FLUORESCENCE REACTION FOR AMINO ACIDS [J].

ROTH, M .

ANALYTICAL CHEMISTRY, 1971, 43 (07) :880-&

[7] POLYMERS CONTAINING ENZYMATICALLY DEGRADABLE BONDS .12. EFFECT OF SPACER STRUCTURE ON THE RATE OF RELEASE OF DAUNOMYCIN AND ADRIAMYCIN FROM POLY[N-(2-HYDROXYPROPYL)-METHACRYLAMIDE] COPOLYMER DRUG CARRIERS INVITRO AND ANTITUMOR-ACTIVITY MEASURED INVIVO [J].

SUBR, V ;

STROHALM, J ;

ULBRICH, K ;

DUNCAN, R ;

HUME, IC .

JOURNAL OF CONTROLLED RELEASE, 1992, 18 (02) :123-132

← 1 →