Simultaneous quantification of palbociclib, ribociclib and letrozole in human plasma by a new LC-MS/MS method for clinical application

Abstract

A novel LC-MS/MS method was developed for the quantification of the new cyclin dependent kinase inhibitors (CDKIs) palbociclib and ribociclib and the aromatase inhibitor letrozole used in combinatory regimen. The proposed method is appropriate to be applied in clinical practice due to the simple and fast sample preparation based on protein precipitation, the low amount of patient sample necessary for the analysis (10 μL) and the total run time of 6.5 min. It was fully validated according to FDA and EMA guidelines on bioanalytical method validation. The linearity was assessed (R 2 within 0.9992-0.9983) over the concentration ranges of 0.3-250 ng/mL for palbociclib, 10-10000 ng/mL for ribociclib and 0.5-500 ng/mL for letrozole that properly cover the therapeutic plasma concentrations. A specific strategy was implemented to reduce the carryover phenomenon, formerly known for these CDKIs. This method was applied to quantify the C min of palbociclib, ribociclib and letrozole in plasma samples from patients enrolled in a clinical study. The same set of study samples was analysed twice in separate runs to assess the reproducibility of the method by means of the incurred samples reanalysis. The results corroborated the reliability of the analyte concentrations obtained with the bioanalytical method, already proved by the validation process. The percentage differences were always within ±10% for all the analytes and the R 2 of the correlation graph between the two quantifications was equal to 0.9994. OPEN ACCESS Citation: Posocco B, Buzzo M, Poetto AS, Orleni M, Gagno S, Zanchetta M, et al. (2020) Simultaneous quantification of palbociclib, ribociclib and letrozole in human plasma by a new LC-MS/MS method for clinical application. PLoS ONE 15(2): e0228822.

Liquid chromatography–tandem mass spectrometric assay for the quantification of CDK4/6 inhibitors in human plasma in a clinical context of drug-drug interaction

“…However, with the exception of the data from the PALOMA trials or from small cohorts, clinicians do not have much information on palbociclib plasma exposure [7]. Our preliminary analysis in 18 patients showed a mean C trough of 88.58 ng/mL, similar to what reported in the PALOMA trials.…”

“…Conversely, very few evidence-based data are available on TDM usefulness for oral targeted therapies used in breast cancer, such as everolimus and lapatinib. Some methods have been validated for the plasma quantification of CDK4/ 6inhibitors, but they are less used in real-life settings [5][6][7]. Therefore, we developed a specific high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method suitable for TDM of palbociclib and ribociclib in real-life settings.…”

Highly Functionalized Modified Metal Oxides Polymeric Sensors for Potentiometric Determination of Letrozole in Commercial Oral Tablets and Biosamples

“…The action of this medication is very specific and does not inhibit the formation of corticosteroids [25]. LTZ was previously quantified using various analytical techniques, including chromatographic separation such as high-performance thin layer chromatography [26], reversed phase liquid chromatography [27,28], liquid chromatography coupled with tandem mass spectrometry [29,30], and capillary zone electrophoresis [31]. Furthermore, different spectrophotometric methods were reported for the determination of LTZ in various media [32][33][34][35][36].…”

Separation and Determination of Process Related Impurities in Palbociclib: A Rp-hplc Study

“…Only few analytical methods were reported for determination of Palbociclib either in dosage forms [6][7][8] or in biological fluids [9][10][11][12] as a single entity or in combination with other drugs. So far no method was reported in the literature for determination of process-related substances of Palbociclib.…”