Electrochemiluminescence immunoassay for quantifying ZMA001 in human serum: method development, validation, and clinical pharmacokinetic application.

Abstract

ZMA001 is a novel human IgG1 monoclonal antibody (mAb) specifically designed to target the N-terminal region of transmembrane lysyl-tRNA synthetase 1 (KARS1), an enzyme implicated in the pathobiology of pulmonary arterial hypertension. The study aimed to develop a bioanalytical method to quantify ZMA001 in human sera to support a phase 1 clinical trial (NCT05967299). An indirect Electrochemiluminescence Immunoassay (ECLIA) method was developed employing KARS1 antigen as the capture reagent and SULFOTAG goat antihuman antibody as the secondary antibody. The method was subsequently validated in accordance with relevant guidelines, including those of the International Council for Harmonization (ICH). The assay's quantification range was established at 0.5-50 µg/mL. The assay was accurate, precise, and selective for the determination of ZMA001 concentrations in human serum. Results revealed that ZMA001 was stable at room temperature for over 4 hours and could withstand multiple freeze-thaw cycles. No prozone/hook effect was apparent in the assay range. Based on preliminary pharmacokinetic data, the average maximum concentration is 41.8 μg/mL while the half-life is about 9.9 days. The method provides a rapid and sensitive approach for the quantitative assessment of ZMA001 in human serum and is well-suited for use in ongoing and future clinical studies.