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\begin{document}

\title{Establishment of a measurement system to evaluate breast milk transfer
of biological agents using dry filter paper: a multi-institutional study}



\author[1]{Jumpei Saito}%
\author[1]{Naho Yakuwa}%
\author[2]{Yoshihiko Hosokawa}%
\author[2]{Hiromi Hamada}%
\author[1]{Tomo Suzuki}%
\author[1]{Haruhiko Sago}%
\author[1]{Kayoko Kaneko}%
\author[1]{Akimasa Yamatani}%
\author[1]{Atsuko Murashima}%
\affil[1]{National Center for Child Health and Development}%
\affil[2]{University of Tsukuba Hospital}%


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  \date{May 25, 2024}


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\begin{abstract}
Aims Information on breastfeeding and the safety of biologics in infants
is lacking due to difficulties in case collection. We evaluated a method
for determining the concentration of biologics in breast milk using a
dry filter method that can simplify the collection, storage, and
transport of breast milk. Methods To generate dried filter paper (DFP)
samples, approximately 30 ?L of breast milk was placed onto a Whatman
903 card and punched out. After extraction, the supernatant was measured
using an enzyme-linked immunosorbent assay. Three concentrations of each
drug were prepared in liquid breast milk (LBM) and DFP samples for
stability testing, which confirmed that samples were stable up to 28
days after storage at 2--8 \selectlanguage{ngerman}ºC or -20 ºC for LBM and at 25±5 ºC for DFP.
LBM and DFP samples were provided by lactating mothers using biologics
during lactation. Drug concentrations were compared. Results Breast milk
was provided by 12 lactating mothers (tocilizumab, n=4; abatacept, n=2;
etanercept, n=1; golimumab, n=1; sarilumab, n=1; and belimumab, n=3).
The accuracy and precision of measurements for the six drugs were within
acceptable limits. After 28 days, concentrations remained at more than
90\% under all storage conditions. The quantitative values of the
provided LBM and DFP samples were similar. The maximum relative infant
dose ranged from 0.09\% to 1.12\%, which was an acceptable range.
Conclusion A method for determining the concentration of biologics using
DFP is expected to help improve pharmacotherapy for lactating women.%
\end{abstract}\selectlanguage{ngerman}%



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