Development of novel extraction and separation methods for the determination of anthracyclines and taxanes simultaneously from biological matrices

摘要

For certain types of advanced cancers patients may be given a combination of an anthracycline and a taxane for chemotherapy treatment. Despite the fact that a mixture of anthracyclines and taxanes may be administered simultaneously to patients and that accurate measurement of drug levels during chemotherapy is proven to be more beneficial to patients, currently no chromatographic method exists for the measurement of any anthracycline and taxane drugs in a single assay. It would be useful to carry out therapeutic drug monitoring (TDM) in order to assess how the patient is metabolising the drugs and to see whether the dosage is working or should be altered. Such information during therapy can be a very important clinical tool for the oncologist, enabling them to change dosage or even drug regimen on an individual basis for patients, improving outcome in the long run.udThis thesis describes the development of two different analytical methods capable of quantifying both drug types in a single assay. The first method employed the use of on-line SPE-LC-UV and this method was then transferred to a mass spectrometric detector for more sensitive monitoring of the drugs. The on-line SPE-LC-MS assay did result in lower limits of detection and was fully automated. The entire method of extraction, separation and detection was achieved on-line by column-switching between an SPE column and an analytical column. The optimum type of switching valve, extraction conditions and separating conditions were evaluated for both methods in order to obtain the highest recovery possible for each target analyte in human serum. Recoveries ranged from 86 to 117% for each analyte in the LC-UV method and from 95 to 113% for most analytes in the LC-MS assay. This research could potentially lead to the introduction of therapeutic drug monitoring in Ireland for cancer patients being treated with anthracyclines or taxanes or both.ud