Epirubicin, olaparib and ribociclib are three anti-tumoral molecules currently used in cancer therapy. Since serum levels of these drugs reveal a large inter-individual variability, validation of a fast, simple and reliable analytical method for quantitative determination of these molecules in human serum, with Therapeutic Drug Monitoring (TDM) purposes would be necessary. Papers in literature describe separation, identification and quantitation of the drugs in pharmaceutical formulas and biological matrices. The large majority of these approaches use protein precipitation for sample pre-treatment, followed by LC separation and tandem-mass-spectrometry (MS/MS) detection. We propose an alternative method using Solid Phase Extraction (SPE) with Oasis PRiME HLB® cartridges followed by high-performance liquid chromatography (HPLC) using a C18 (4.6 × 50 mm) column. A gradient mobile phase with 0.1% formic acid/acetonitrile was utilized. MS detection in single ion recording (SIR) mode was employed. A 13-minutes run-time analysis, including column re-equilibration was assessed. Data for all molecules were validated according to ICH Guidelines. Calibration curves for all analytes were linear with correlation coefficient larger than 0.997. Values for precision were less than 6%. The method was applied on serum samples from patients up-taking the drugs, proving its suitability in TDM assisted adjustment of doses in therapy.

Sorafenib and nilotinib are two tyrosine kinase inhibitors (TKIs) used in the treatment of cancer. Plasmatic levels of the drugs show an important variability, so determining plasma concentration of the drugs, benefits in cancer treatment can be improved. Most papers published so far in the literature use protein precipitation followed by liquid chromatography tandem mass-spectrometry (LC-MS/MS) as separation and detection method. With this work, we propose an alternative method for the analysis of both TKIs in human plasma. Solid phase extraction (SPE) involving Oasis PRiME HLB (R) cartridges was our choice for plasma "clean-up" procedure. Extraction recoveries were at least 85%. Chromatography was performed by an ultra-high-performance liquid chromatographic system (UHPLC), using a C18 (4.6 x 50 mm) column and a mobile phase consisting of ammonium acetate/acetic acid-acetonitrile gradient elution. Detector was a simple mass spectrometer (MS) in Single Ion Recording (SIR) mode. Intra-and inter-day precision data for both TKIs were 3.8 7.6% and 4.5 8.8% for sorafenib and nilotinib, respectively. Sorafenib and nilotinib calibration curves were linear between 500 and 20000 ng/mL and 5 and 5000 ng/mL respectively, with correlation coefficients higher than 0.998. Analytes were determined in a 15 min run-time. The validated LC-MS method was applied in real human plasma routine analysis. This method may improve dose adjustment of the drugs in patients involved in cancer therapy.

The class of tyrosine kinase inhibitors (TKIs) is represented by a group of compounds which are currently used in the treatment of different types of cancer. As plasma concentration profiles of these drugs reveal a large interindividual variability, therapeutic drug monitoring (TDM) might be necessary to adjust the therapeutic protocol. With this purpose, we developed and validated a simple and accurate method for determining plasma concentrations for two TKIs. Solid phase extraction (SPE) using Oasis PRiME HLB (R) cartridges was used for plasma sample preparation procedure. The method provided clean extracts with a recovery extraction of more than 85%. Separation was achieved by high-performance liquid chromatography (HPLC), using a C18 (4.6 x 50 mm) column, with a gradient elution of ammonium formate-acetonitrile as mobile phase. Detection was performed by mass spectrometry (MS) in Single Ion Recording (SIR) mode. Intra-day and interday precision data for both analytes were 3.8 - 7.2% and 3.6 - 7.4%, respectively. Calibration curves were both linear between 2 and 400 ng/mL with a correlation coefficient higher than 0.998. The LC-MS method was used to quantify both TKIs in human plasma in routine analysis. The method was applied to TDM of ibrutinib and ruxolitinib and may help physicians for dose adjustment.

Palbociclib and abemaciclib are two cyclin-dependent kinases 4 and 6 used for breast cancer treatment. Levels of these medicines present a significant interindividual variability, so monitoring those concentrations might be necessary in therapy. Most of the methods presented so far in the literature use simple protein precipitation of plasma proteins as sample preparation method followed by direct injection of the supernatant into the LC instrument, preceded or not by a simple filtration step. Within that approach, the probability of injecting proteins in the chromatographic system is increased. With the purpose of obtaining a cleaner extract of the drugs, we developed and validated a simple and accurate LC-MS method for determining palbociclib and abemaciclib in human plasma. Solid phase extraction (SPE) using Oasis PRiME HLB® cartridges was used for plasma sample preparation. The method provided clean extracts with a recovery extraction higher than 85% for both compounds. Separation was achieved by high-performance liquid chromatography (HPLC), using a C18 (4.6 × 50 mm) column, with a gradient elution of ammonium acetate/acetic acid-acetonitrile as the mobile phase. Detection was performed by mass spectrometry (MS) in single ion recording (SIR) mode. Intra-day and inter-day precision data for both analytes were 3.8–7.2% and 3.6–7.4%, respectively. Calibration curves were both linear between 2 and 400 ng/mL with a correlation coefficient higher than 0.998. The LC-MS method can be used to quantify the drugs in human plasma in routine analysis. The method proved to be useful in determining real plasma levels in patients involved in cancer therapy. Drug concentrations were determined in a 10 min run-time, including re-equilibration of the column.