Jelle Broeders

Oncode Institute

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G.R. Davies

Vrije Universiteit Amsterdam

Alfred H. Schinkel

The Netherlands Cancer Institute

Alejandra Martínez-Chávez

The Netherlands Cancer Institute

Lisette M. Kootker

Vrije Universiteit Amsterdam

Isabella C.C. von Holstein

Vrije Universiteit Amsterdam

Daniel J. Wescott

Texas State University

Hilde Rosing

The Netherlands Cancer Institute

Jos H. Beijnen

The Netherlands Cancer Institute

Hayley L. Mickleburgh

University of Amsterdam

Maria C. Lebre

The Netherlands Cancer Institute

Cooperative Institutions

The Netherlands Cancer Institute

Oncode Institute

Slotervaartziekenhuis

Vrije Universiteit Amsterdam

University of Amsterdam

Leiden University

Utrecht University

Institute of Geochemistry

PharmaMar (Spain)

Texas State University

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The effects of decomposition and environment on antemortem H-Pb-Sr isotope compositions and degradation of human scalp hair: Actualistic taphonomic observations

Forensic Science International (2020)

Lisette M. Kootker Isabella C.C. von Holstein Jelle Broeders Daniel J. Wescott G.R. Davies

Multi-isotope analysis (e.g., Sr–Pb–O–H–C–N) of human scalp hair is routinely used in forensic investigations of human remains to constrain the geographic origin of unidentified bodies, and to investigate antemortem mobility patterns. However, while it is known that postmortem processes can affect the preservation of, or even overprint, the biogenic isotopic signatures in hair, the speed and nature of these processes have rarely been studied. This study investigates the effects of decomposition and environment on the H–Pb–Sr isotope compositions of human hair as well as the relationship between structural hair shaft degradation and isotopic signature change over time. Human scalp hair samples from four body donations were collected at different stages throughout gross body decomposition. The willed-donated bodies were placed to decompose outdoors at the Forensic Anthropology Research Facility (FARF) at Texas State University. Hair fibers from two of the donations were examined using scanning electron microscopy (SEM) and high-resolution light microscopy (HRLM). Chemical and microbiological degradation of hair fibers occurred rapidly after placement of the body outdoors. Measurements of scalp hair isotopic composition demonstrated that H–Pb–Sr isotope ratios were altered within days after environmental exposure, presumably by deposition, leaching and/or exchange with the local bioavailable soil, and vapor. The degree of physical hair degradation and changes in H–Pb–Sr isotope composition were not correlated. We conclude that antemortem isotopic H–Pb–Sr isotope ratios are difficult to recover in hairs derived from decomposing whole bodies.

Isotopic signature

Taphonomy

10.1016/j.forsciint.2020.110336

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Citations (14)

Development and validation of an LC-MS/MS method for the quantitative analysis of milciclib in human and mouse plasma, mouse tissue homogenates and tissue culture medium

Journal of Pharmaceutical and Biomedical Analysis (2020)

Alejandra Martínez-Chávez Matthijs M. Tibben Jelle Broeders Hilde Rosing Alfred H. Schinkel

Milciclib is a promising cyclin-dependent kinase inhibitor currently in phase II clinical trials to treat several types of cancer. The first bioanalytical method for the quantitative analysis of milciclib in several biomatrices using liquid chromatography-tandem mass spectrometry is described here. This method was fully validated in human plasma according to FDA and EMA guidelines, and partially validated in mouse plasma, homogenates of mouse brain, kidney, liver, small intestine, spleen, and tissue culture medium. Palbociclib, an analog compound, was used as internal standard. A simple and fast sample pre-treatment by protein precipitation with acetonitrile was used, leading to efficient extraction of the analyte with recoveries between 95–100%. Chromatographic separation was achieved with a C18 analytical column and a gradient elution using 10 mM ammonium bicarbonate in water and 10 mM ammonium bicarbonate in water-methanol (1:9, v/v). This assay was selective, accurate, precise and linear in the concentration range of 1−1000 ng/mL. Moreover, samples above the upper limit of quantification can be integrally diluted up to 10-fold prior to analysis. The use of human plasma as a surrogate matrix to quantify milciclib in tissue culture medium and mouse matrices resulted in acceptable accuracy and precision, however tissue culture medium samples required a dilution with human plasma prior the pre-treatment. All performance parameters of the method complied with the acceptance criteria recommended by the guidelines, except for the carry-over, which was slightly above (22.9% of the lower limit of quantification) the recommended percentage (20%). Therefore, additional measures were taken to assure data integrity. Stability of milciclib in all matrices was evaluated, and in some matrices the analyte was unstable under the tested conditions. It is therefore recommended to keep these samples as briefly as possible at room temperature during the pre-treatment, and to store them at –70 °C to avoid analyte degradation. This method was successfully applied to support preclinical pharmacokinetic studies of milciclib.

Bioanalysis

Protein precipitation

Solid phase extraction

Ammonium bicarbonate

Quantitative Analysis

Sample Preparation

Standard curve

10.1016/j.jpba.2020.113516

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Citations (8)

The role of drug efflux and uptake transporters ABCB1 (P-gp), ABCG2 (BCRP) and OATP1A/1B and of CYP3A4 in the pharmacokinetics of the CDK inhibitor milciclib

European Journal of Pharmaceutical Sciences (2021)

Alejandra Martínez-Chávez Jelle Broeders Maria C. Lebre Matthijs T. Tibben Hilde Rosing

Abcg2

Fexofenadine

CYP3A

Efflux

10.1016/j.ejps.2021.105740

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Citations (7)

Reprint of: The effects of decomposition and environment on antemortem H-Pb-Sr isotope compositions and degradation of human scalp hair: Actualistic taphonomic observations

Forensic Science International (2020)

Lisette M. Kootker Isabella C.C. von Holstein Jelle Broeders Daniel J. Wescott G.R. Davies

Multi-isotope analysis (e.g., Sr-Pb-O-H-C-N) of human scalp hair is routinely used in forensic investigations of human remains to constrain the geographic origin of unidentified bodies, and to investigate antemortem mobility patterns. However, while it is known that postmortem processes can affect the preservation of, or even overprint, the biogenic isotopic signatures in hair, the speed and nature of these processes have rarely been studied. This study investigates the effects of decomposition and environment on the H-Pb-Sr isotope compositions of human hair as well as the relationship between structural hair shaft degradation and isotopic signature change over time. Human scalp hair samples from four body donations were collected at different stages throughout gross body decomposition. The willed-donated bodies were placed to decompose outdoors at the Forensic Anthropology Research Facility (FARF) at Texas State University. Hair fibres from two of the donations were examined using scanning electron microscopy (SEM) and high-resolution light microscopy (HRLM). Chemical and microbiological degradation of hair fibres occurred rapidly after placement of the body outdoors. Measurements of scalp hair isotopic composition demonstrated that H-Pb-Sr isotope ratios were altered within days after environmental exposure, presumably by deposition, leaching and/or exchange with the local bioavailable soil, and vapour. The degree of physical hair degradation and changes in H-Pb-Sr isotope composition were not correlated. We conclude that antemortem isotopic H-Pb-Sr isotope ratios are difficult to recover in hairs derived from decomposing whole bodies.

Taphonomy

Isotopic signature

10.1016/j.forsciint.2020.110463

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Citations (5)