A new dried blood spot LC-MS/MS method for therapeutic drug monitoring of palbociclib, ribociclib, and letrozole in patients with cancer was written by Poetto, Ariana Soledad;Posocco, Bianca;Gagno, Sara;Orleni, Marco;Zanchetta, Martina;Iacuzzi, Valentina;Canil, Giovanni;Buzzo, Mauro;Montico, Marcella;Guardascione, Michela;Basile, Debora;Pelizzari, Giacomo;Alberti, Martina;Gerratana, Lorenzo;Puglisi, Fabio;Toffoli, Giuseppe. And the article was included in Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences in 2021.Electric Literature of C23H30N8O This article mentions the following:
Therapeutic drug monitoring TDM is strongly suggested to define the proper drug dosage to overcome inter- and intra-patient variability in drug exposure, which is typically observed with oral anticancer agents, such as palbociclib PALBO, ribociclib RIBO and letrozole LETRO, all approved for the treatment of HR+, HER2- locally advanced or metastatic breast cancer BC. Optimal TDM implementation requires a blood sampling organization that can be hampered by limited availability of health and laboratory personnel. Dried Blood Spot DBS sampling is proposed to overcome such limitations. The aim of this work was the development of a new LC-MS/MS method to analyze DBS samples containing PALBO, RIBO, and LETRO. Analytes extraction from DBS was performed by adding a methanolic solution containing the corresponding internal standards LC-MS/MS anal. was performed using a LC Nexera Shimadzu system coupled with an API 4000 QTrap SCIEX mass spectrometer. The chromatog. separation was performed on a Luna Omega Polar C18 column Phenomenex. The method was applied to 38 clin. samples collected by finger prick. The influence of hematocrit and spot size, sample homogeneity, stability, and correlation between finger prick and venous DBS measurement were assessed. The anal. validation was performed according to EMA and FDA guidelines. The anal. range of the method was 1 to 250 ng/mL for PALBO, 40 to 10000 ng/mL for RIBO, and 2 to 500 ng/mL for LETRO, where linearity was assessed, obtaining mean coefficients of determination R2 of 0.9979 for PALBO, 0.9980 for RIBO, and 0.9987 for LETRO. The LC-MS/MS method runtime was 6.6 min. Incurred sample reanal. demonstrated reproducibility, as the percentage difference between the two quantifications was lower than 20% for 100% of PALBO, 81.8% of RIBO, and 90.9% of LETRO paired samples. Intra- and inter-day precision CV % was lower than 11.4% and intra- and inter-day accuracy was between 90.0 and 106.5%. DBS sample stability at room temperature was confirmed for 2.5 mo. A pos. correlation was observed between DBS and plasma concentrations for the 3 drugs, Lins concordance correlation coefficients obtained by DBS normalization applying a selected strategy were 0.958 for PALBO, 0.957 for RIBO, and 0.963 for LETRO. In conclusion, a fast, easy, and reproducible DBS LC-MS/MS method for the simultaneous quantification of palbociclib; ribociclib and letrozole was developed to be used in clin. practice. In the experiment, the researchers used many compounds, for example, 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3Electric Literature of C23H30N8O).
7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3) belongs to piperazine derivatives. Piperazine was first introduced as an anthelmintic in 1953. Piperazine compounds mediate their anthelmintic action by generally paralyzing parasites, allowing the host body to easily remove or expel the invading organism. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.Electric Literature of C23H30N8O
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics