The anticancer drug imatinib is often involved in therapeutic drug monitoring (TDM) studies aimed at improving the treatment of several forms of leukemia and gastrointestinal stromal tumors (GIST). To further implement the TDM of imatinib in the clinical practice, we developed a detection assay by using a ssDNA aptamer, which demonstrated an excellent selectivity and was not affected by interference from components of human plasma samples. The efficient binding of imatinib to the aptamer was demonstrated by means of surface plasmon resonance (SPR) analysis, which allowed the development of a quantitative assay in the concentration range between 400 and 6000 ng mL-1 (0.7-10 µM), where a lower limit of quantification (LLOQ) of 400 ng mL-1 was achieved. The precision of the assay was found within 12.0%, whereas the accuracy was in a range between 97.1 and 101.5%. The sample preparation procedure displayed a recovery in the range 48.8-52.8%. Solid validation data were collected according to regulatory guidelines and the method was compared with standard analytical techniques, leading to the development of a feasible aptasensor for the TDM of patients administered with imatinib.

An SPR investigation toward the therapeutic drug monitoring of anticancer drug imatinib with selective aptamers operating in human plasma

Anna Meneghello;Federico Polo
Supervision
;
2021-01-01

Abstract

The anticancer drug imatinib is often involved in therapeutic drug monitoring (TDM) studies aimed at improving the treatment of several forms of leukemia and gastrointestinal stromal tumors (GIST). To further implement the TDM of imatinib in the clinical practice, we developed a detection assay by using a ssDNA aptamer, which demonstrated an excellent selectivity and was not affected by interference from components of human plasma samples. The efficient binding of imatinib to the aptamer was demonstrated by means of surface plasmon resonance (SPR) analysis, which allowed the development of a quantitative assay in the concentration range between 400 and 6000 ng mL-1 (0.7-10 µM), where a lower limit of quantification (LLOQ) of 400 ng mL-1 was achieved. The precision of the assay was found within 12.0%, whereas the accuracy was in a range between 97.1 and 101.5%. The sample preparation procedure displayed a recovery in the range 48.8-52.8%. Solid validation data were collected according to regulatory guidelines and the method was compared with standard analytical techniques, leading to the development of a feasible aptasensor for the TDM of patients administered with imatinib.
2021
146
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10278/3733966
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