Simultaneous high-performance liquid chromatographic determination of a glucuronyl prodrug of doxorubicin, doxorubicin and its metabolites in human lung tissue.
A rapid and sensitive method was developed for the simultaneous determination of the new doxorubicin glucuronide prodrug HMR 1826, the parent drug doxorubicin and its metabolites in human lung tissue samples. Homogenization of frozen tissue samples with the micro-dismembrator was followed by a silver nitrate precipitation step. By removing the exceeding silver ions with sodium chloride further purification steps could be omitted. Compounds were separated by isocratic high-performance liquid chromatography on a LiChrospher 100 RP18 column and a mobile phase consisting of citric acid buffer-acetonitrile-methanol-tetrahydrofuran within 30 min and quantified with fluorescence detection. The method showed good recoveries for all compounds (86-99%) and a linear calibration range of 20 ng/g-80 microg/g for doxorubicin and 1-600 microg/g for HMR 1826.
Mürdter
T E
TE
Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart, Germany.
Sperker
B
B
Bosslet
K
K
Fritz
P
P
Kroemer
H K
HK
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000032:analysis* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000032:analysis* / Q000378:metabolism; D005965:Glucuronates / Q000032:analysis*; D006801:Humans; D008168:Lung / Q000737:chemistry*; D008175:Lung Neoplasms / Q000737:chemistry; D010477:Perfusion; D011355:Prodrugs / Q000032:analysis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence; D013552:Swine
D000903:Antibiotics, Antineoplastic; D005965:Glucuronates; C114198:N-(4-glucuronyl-3-nitrobenzyloxycarbonyl)doxorubicin; D011355:Prodrugs; D004317:Doxorubicin