A simple and fast LC-MS/MS method for the routine measurement of cabozantinib, olaparib, palbociclib, pazopanib, sorafenib, sunitinib and its main active metabolite in human plasma

Jolibois, Julia; Schmitt, Antonin; Royer, Bernard

doi:10.1016/j.jchromb.2019.121844

Cited by 42 publications

(56 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Palbociclib blood samples were analyzed by liquid chromatography-mass spectrometry using the method described by Jolibois et al [ 11 ] which allows the simultaneous measurement of palbociclib, olaparib, cabozantinib, pazopanib, sorafenib, sunitinib and desethyl-sunitinib. After blood collection, samples were rapidly centrifuged and frozen until the analysis.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetic/Pharmacodynamic Model of Neutropenia in Real-Life Palbociclib-Treated Patients

et al. 2021

Self Cite

View full text Add to dashboard Cite

Palbociclib is an oral CDK4/6 inhibitor indicated in HR+/HER2- advanced or metastatic breast cancer in combination with hormonotherapy. Its main toxicity is neutropenia. The aim of our study was to describe the kinetics of circulating neutrophils from real-life palbociclib-treated patients. A population pharmacokinetic (popPK) model was first constructed to describe palbociclib pharmacokinetic (PK). Individual PK parameters obtained were then used in the pharmacokinetic/pharmacodynamic (PK/PD) model to depict the relation between palbociclib concentrations and absolute neutrophil counts (ANC). The models were built with a population of 143 patients. Palbociclib samples were routinely collected during therapeutic drug monitoring, whereas ANC were retrospectively retrieved from the patient files. The optimal popPK model was a mono-compartmental model with a first-order absorption constant of 0.187 h−1 and an apparent clearance Cl/F of 57.09 L (32.8% of inter individuality variability (IIV)). The apparent volume of distribution (1580 L) and the lag-time (Tlag: 0.658 h) were fixed to values from the literature. An increase in creatinine clearance and a decrease in alkaline phosphatase led to an increase in palbociclib Cl/F. To describe ANC kinetics during treatment, Friberg’s PK/PD model, with linear drug effect, was used. Parameters estimated were Base (2.92 G/L; 29.6% IIV), Slope (0.0011 L/µg; 28.8% IIV), Mean Transit Time (MTT; 5.29 days; 17.9% IIV) and γ (0.102). The only significant covariate was age on the initial ANC (Base), with lower ANC in younger patients. PK/PD model-based simulations show that the higher the estimated CressSS (trough concentration at steady state), the higher the risk of developing neutropenia. In order to present a risk lower than 20% to developing a grade 4 neutropenia, the patient should show an estimated CressSS lower than 100 µg/L.

show abstract

Section: Methodsmentioning

confidence: 99%

Pharmacokinetic/Pharmacodynamic Model of Neutropenia in Real-Life Palbociclib-Treated Patients

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…The samples were rapidly centrifuged and frozen. They were assayed using a Liquid chromatography-tandem mass spectrometry (LC/MS-MS) validated method, as previously described [10]. Briefly, after alkalinization with NaOH, an extraction was performed with ethyl acetate.…”

Section: Methodsmentioning

confidence: 99%

Population Pharmacokinetics of Palbociclib in a Real-World Situation

et al. 2021

Self Cite

View full text Add to dashboard Cite

Palbociclib is an oral cyclin-dependent kinase inhibitor that is used in combination with aromatase inhibitors in the treatment of postmenopausal women with metastatic breast cancer. Its metabolism profile is associated with an important interpatient variability. We performed a population pharmacokinetics study of palbociclib in women routinely followed in a cancer center. One hundred and fifty-one samples were analyzed. The sampling times after administration ranged from 0.9 to 75 h and the samples were taken between 1 and 21 days after the beginning of the palbociclib cycle. Palbociclib was determined using a validated mass spectrometry method. The best model that described the concentrations was a one-compartment model with first-order absorption and an absorption lag time. Interindividual variability could only be estimated on the clearance and the first-order absorption. Creatinine clearance was found to be a significant covariate for the apparent clearance. No significant covariates could be observed with the first-order absorption. First-order absorption and absorption lag times were difficult to assess because of the constraints linked to the real-world setting due to the small number of samples used during the absorption process. However, palbociclib apparent clearance was satisfactorily estimated. Population pharmacokinetics (POP PK) with palbociclib could help to optimize dosing.

show abstract

“…The molecular docking studies are useful for determining the binding capacity of drug molecules and their DPs towards the corresponding protein. Supported extensive literature search, LC-MS-MS [12][13][14][15][16][17][18][19] and LC techniques 20 were reported for therapeutic drug monitoring investigations in humans, animals and Pharmaceutical formulations. Hence, no method reported thus far for the characterization of Palbociclib together with DPs.…”

Section: Introductionmentioning

confidence: 99%

Method Development Combined with in silico Therapeutic and Toxicology Studies on Palbociclib and its Degradation Products to Assist in Discovery of New Molecule

Reehana

Sujana

2021

IJPI

View full text Add to dashboard Cite

Background: Palbociclib is anti-cancer drug which interacts with cyclindependent kinase. There are no methods repoRTed for the characterization of palbociclib together with degradation products (DPs). The main aim of the study is to develop method combined with in silico therapeutic and toxicology studies on palbociclib and its DPs which assist in discovery of new molecule. Methods: A new analytical method was developed for the identification, characterization of palbociclib and DPs formed when subjected to forced degradation, using symmetry C 18 column, 150mm x 4.6mm, 3.5µm in isocratic mode with acetonitrile: formic acid (0.1%) (50:50). In silico toxicity for drugs and DPs were predicted using the Swiss ADME web tool and StarDrop Derek Nexus software for all DPs. Results: Validation: LOD and LOQ were 0.01 and 0.1 μg/ml. which shows accuracy data at three different concentrations of 50, 100, and 150 % in triplicate analysis. The % RSD for intra-day and intermediate precision was 0.47% and 0.33%, respectively, indicating the method was sufficiently precise. Mass spectrums (LC-MS/MS) of drug with m/z 447(RT= 4.075 min), DPI with [M+H] + at m/z 503(RT= 1.328 min), DPII with [M+H] + at m/z 540 (RT= 2.371 min), DPIII with m/z 46 (RT= 3.741 min) are reported. In docking studies, PS2 showed a higher docking score -12.289. Conclusion: The drug was found to degrade under forced degradation and DPs are characterized. All the DPs were found to be toxic except the major fragment ions (PS2), showed higher binding affinity than drug without toxicity. This is the lead molecule for further drug discovery.

show abstract

A simple and fast LC-MS/MS method for the routine measurement of cabozantinib, olaparib, palbociclib, pazopanib, sorafenib, sunitinib and its main active metabolite in human plasma

Cited by 42 publications

References 37 publications

Pharmacokinetic/Pharmacodynamic Model of Neutropenia in Real-Life Palbociclib-Treated Patients

Pharmacokinetic/Pharmacodynamic Model of Neutropenia in Real-Life Palbociclib-Treated Patients

Population Pharmacokinetics of Palbociclib in a Real-World Situation

Method Development Combined with in silico Therapeutic and Toxicology Studies on Palbociclib and its Degradation Products to Assist in Discovery of New Molecule

Contact Info

Product

Resources

About