Bioanalytical liquid chromatography-tandem mass spectrometric assay for the quantification of the ALK inhibitors alectinib, brigatinib and lorlatinib in plasma and mouse tissue homogenates

Publication date: Available online 19 August 2018Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Rolf W. Sparidans, Wenlong Li, Alfred H. Schinkel, Jan H.M. Schellens, Jos H. BeijnenAbstractSeveral second and third generation ALK inhibitors have been introduced in recent years. A bioanalytical assay for simultaneous quantification of alectinib, brigatinib, and lorlatinib was developed and validated for human plasma. The method was also partially validated for diluted mouse plasma and tissue homogenates of brain, liver, kidney, and spleen. Samples (40 µl) were pretreated in a 96-well plate by protein precipitation with acetonitrile containing the internal standard [2H8]-alectinib. After chromatographic separation on an ethylene bridged octadecyl silica column by gradient elution at 600 µl/min using 1% (v/v) formic acid (in water) and acetonitrile, compounds were ionized by a turbo electrospray and monitored by selected reaction monitoring on a triple quadrupole mass spectrometer. Validation was performed in a 2 − 2000 ng/ml concentration range for alectinib and lorlatinib and a 4 − 4000 ng/ml range for brigatinib. Precisions (within − day and between − day) were in the range 2.2 − 15.0% and accuracies were in between 87.2 and 110.2% for all matrices and levels. Compounds were sufficiently stable under most investigated conditions. Results of a pilot pharmacokinetic and tissue distribution...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research

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Source: European Journal of Obstetrics and Gynecology and Reproductive Biology - Category: OBGYN Source Type: research
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Source: Current Nutrition and Food Science - Category: Nutrition Source Type: research
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Source: Current Nutrition and Food Science - Category: Nutrition Source Type: research
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Source: Current Nutrition and Food Science - Category: Nutrition Source Type: research
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Source: Current Nutrition and Food Science - Category: Nutrition Source Type: research
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Source: Current Nutrition and Food Science - Category: Nutrition Source Type: research
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