Patent DE-102012014614-A1 (DE)
Title: Determining concentration of chemotherapeutic agent in biological fluid sample of subject after beginning of administration of the agent to subject, comprises separating proteins of sample, and measuring fluorescence signal of sample
Inventor: ECKES JUERGEN
IPC: G01N33/68
Filed: 2012-07-24
Abstract: Determining concentration of a chemotherapeutic agent and its optionally present metabolites in a biological fluid sample of a subject at a time of 0-60 minutes after the beginning of the administration of the chemotherapeutic agent or its salt to the subject, comprises (i) separating proteins present in the fluid sample by (a) precipitating the proteins with a precipitating reagent, and centrifuging or filtering the fluid sample, (b) dialyzing or (c) carrying out ultrafiltration, and (ii) measuring a fluorescence signal originating from the fluid sample by irradiating with excitation light. Determining concentration of a chemotherapeutic agent comprising doxorubicin, epirubicin, idarubicin, daunorubicin, etoposide, 5-fluorouracil, fludarabine or chlorambucil and its optionally present metabolites in a biological fluid sample of a subject at a time of 0-60 minutes after the beginning of the administration of the chemotherapeutic agent or its salt to the subject, comprises (i) separating proteins present in the fluid sample by (a) precipitating the proteins with a precipitating reagent comprising trichloroacetic acid, methanol, ethanol, acetonitrile and/or zinc sulfate, and centrifuging or filtering the fluid sample, (b) dialyzing or (c) carrying out ultrafiltration, and (ii) measuring a fluorescence signal originating from the fluid sample by irradiating with excitation light, after protein separation. The method does not comprise chromatographic- or electrophoretic steps, or liquid-liquid extraction. Independent claims are also included for: (1) ex-vivo method for determining an optimum individual dosage of the chemotherapeutic agent or its salt, comprising (A) determining the concentration of the chemotherapeutic agent and its optionally present metabolites in at least two biological fluid samples of the subject, by the above method, where the biological fluid sample is collected at different times after beginning the administration of the chemotherapeutic agent or its salt to the subject, and (B) calculating the optimal individual dosing from the data obtained in the step (i), which is to be administered for achieving a predetermined concentration of the chemotherapeutic agent and its optionally present metabolites in the biological fluid of the subject; and (2) an infusion apparatus for administering the chemotherapeutic agent or its salts to the subject, comprising (i) a reservoir which comprises the chemotherapeutic agent or its salt, (ii) a dosage unit which regulates the addition of the quantity of the chemotherapeutic agent or its salt per unit time, (iii) a delivery unit for administering the chemotherapeutic agent or its salt from the reservoir to the subject, (iv) a recovery unit for obtaining at least one biological fluid sample of the subject, (v) an analysis unit for determining the concentration of the chemotherapeutic agent and its optionally present metabolites in the biological fluid sample using the above method, and (vi) a control unit for controlling the dosage unit depending on specific concentration in the analysis unit.