A new comprehensive technique of catheterisation, blood sampling, sample preparation and sample analysis by means of high-pressure liquid chromatography for pharmacokinetic studies with estradiol-linked nitrosoureas and their metabolites.
Estradiol-linked nitrosoureas are offering new perspectives in the antineoplastic chemotherapy of estradiol-receptor positive mammary carcinomas. In such a molecule estradiol has the function of a carrier which brings about a specific accumulation of the anticancer drug in estradiol-receptor containing tumor cells. However, there is only little knowledge about the pharmacokinetic behavior of this new group of anticancer agents. For that reason a new comprehensive technique of catheterisation, blood sampling, sample preparation and sample analysis with high-pressure liquid chromatography (HPLC) for preclinical pharmacokinetic studies with estradiol-linked nitrosoureas and their metabolites has been developed. N-(2-Chloroethyl)-N-nitroso-carbamoyl-L-alanine-estradiol-17-ester (CNC-alanine-estradiol-17-ester) and N-(2-chloroethyl)-N-nitroso-carbamoyl-L-alanine (CNC-alanine) were used as test compounds. The drugs were tested in female Sprague-Dawley rats with chemically induced mammary carcinomas. The laboratory animals were supplied with two catheters prior to the pharmacokinetic experiments. The blood samples were drawn from the vena cava catheter after the drug had been applied through a vena jugularis catheter. The compounds were extracted from plasma with C18 silicagel reversed phase cartridges. The clean-up technique delivered clear samples only slightly contaminated with the biological matrix. The recovery from plasma was 75 +/- 5% for the hormone-linked CNC-alanine-estradiol-17-ester and 70 +/- 5% for the unlinked CNC-alanine. The analysis was carried out by means of HPLC.(ABSTRACT TRUNCATED AT 250 WORDS)
Betsch
B
B
Institute for Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.
Berger
M R
MR
Spiegelhalder
B
B
D000409:Alanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D002404:Catheterization / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D004958:Estradiol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D009588:Nitrogen Mustard Compounds / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D013048:Specimen Handling / Q000379:methods*; D014684:Venae Cavae
D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; D004958:Estradiol; C058788:N-(2-chloroethyl)-1-nitrosocarbamoylalanine; C056364:1-(2-chloroethyl)-1-nitrosocarbamoylalanine estradiol-17-ester; D000409:Alanine