Bioanalytical assay for the quantification of the ALK inhibitor lorlatinib in mouse plasma using liquid chromatography-tandem mass spectrometry. 2018

Claudia Spatari, and Wenlong Li, and Alfred H Schinkel, and Gaetano Ragno, and Jan H M Schellens, and Jos H Beijnen, and Rolf W Sparidans
Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology & Clinical Pharmacology, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Polifunzionale, 87036 Rende, Italy. Electronic address: claudia.spatari@unical.it.

A bio-analytical assay for the first third generation ALK inhibitor lorlatinib in mouse plasma was developed and validated. Ten-μl plasma samples were prepared by adding rucaparib as the internal standard and precipitation of the plasma proteins. For LC-MS/MS analysis, compounds were eluted at 0.5 mL/min and separated on a 3-μm particle-size, polar embedded octadecyl silica column by gradient elution using 0.1% of formic acid (in water) and methanol. Compounds were monitored with positive electrospray ionization using a triple quadrupole mass spectrometer in selected reaction monitoring mode. The assay was fully validated in the 2-2000 ng/mL calibration range. Within-day (8.0-11.6%) and between-day (10.0-15.0%) precisions and accuracies (99.0-113.3%) were within acceptable range. Plasma samples were deemed stable for 6 h at ambient temperature, during three freeze-thaw cycles and for 2 months at -30 °C. Finally, the new assay was applied successfully to pilot pharmacokinetic studies in male and female wild-type mice.

UI MeSH Term Description Entries
D007769 Lactams Cyclic AMIDES formed from aminocarboxylic acids by the elimination of water. Lactims are the enol forms of lactams. Lactam,Lactim,Lactims
D011720 Pyrazoles Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
D002853 Chromatography, Liquid Chromatographic techniques in which the mobile phase is a liquid. Liquid Chromatography
D004355 Drug Stability The chemical and physical integrity of a pharmaceutical product. Drug Shelf Life,Drugs Shelf Lives,Shelf Life, Drugs,Drug Stabilities,Drugs Shelf Life,Drugs Shelf Live,Life, Drugs Shelf,Shelf Life, Drug,Shelf Live, Drugs,Shelf Lives, Drugs
D005260 Female Females
D000077548 Anaplastic Lymphoma Kinase A receptor tyrosine kinase that is essential for development and differentiation of the nervous system in response to secreted growth factors. It phosphorylates the first tyrosine of the Y-x-x-x-Y-Y motif of targets that include PROTO-ONCOGENE PROTEINS C-CBL; INSULIN RECEPTOR SUBSTRATE-1; and MITOGEN-ACTIVATED PROTEIN KINASES, leading to activation of the MAPK signaling pathway and cell proliferation. A chromosomal aberration involving the ALK gene results in its constitutive expression in some cases of NON-HODGKIN LYMPHOMA. ALK Kinase,ALK Tyrosine Kinase Receptor,Anaplastic Lymphoma Receptor Tyrosine Kinase,CD246 Antigen,NPM-ALK,Nucleophosmin-Anaplastic Lymphoma Kinase,Nucleophosmin Anaplastic Lymphoma Kinase
D000631 Aminopyridines Pyridines substituted in any position with an amino group. May be hydrogenated but must retain at least one double bond. Aminopyridine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012680 Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed) Specificity,Sensitivity,Specificity and Sensitivity
D015203 Reproducibility of Results The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results. Reliability and Validity,Reliability of Result,Reproducibility Of Result,Reproducibility of Finding,Validity of Result,Validity of Results,Face Validity,Reliability (Epidemiology),Reliability of Results,Reproducibility of Findings,Test-Retest Reliability,Validity (Epidemiology),Finding Reproducibilities,Finding Reproducibility,Of Result, Reproducibility,Of Results, Reproducibility,Reliabilities, Test-Retest,Reliability, Test-Retest,Result Reliabilities,Result Reliability,Result Validities,Result Validity,Result, Reproducibility Of,Results, Reproducibility Of,Test Retest Reliability,Validity and Reliability,Validity, Face

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