Detection of recombinant erythropoietin biosimilar Jimaixin™ after administration in healthy subjects

• Published in: Drug testing and analysis Vol. 14; no. 1; p. 72
• Main Authors: Martin, Laurent, Kafi, Rafik, Zhou, Xinmiao, Zhang, Lisi, Ericsson, Magnus, Marchand, Alexandre
• Format: Journal Article
• Language: English
• Published: England 01.01.2022
• Subjects: Administration, Intravenous; Adult; Biosimilar Pharmaceuticals - administration & dosage; Biosimilar Pharmaceuticals - analysis; Biosimilar Pharmaceuticals - pharmacokinetics; Doping in Sports - prevention & control; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel - methods; Erythropoietin - administration & dosage; Erythropoietin - analysis; Erythropoietin - pharmacokinetics; Humans; Male; Recombinant Proteins; Substance Abuse Detection - methods; Time Factors; doping detection; SDS-PAGE; EPO biosimilar; Jimaixin; IEF-PAGE
• ISSN: 1942-7611
• DOI: 10.1002/dta.3143

Jimaixin™ (Jintan Ltd, China) is a biosimilar of recombinant erythropoietin (rEPO) now authorized for therapeutic application in China. With a risk of abuse by athletes, a clear evaluation of its detection using the electrophoretic methods in use in antidoping laboratories was necessary. In a previous work, we showed that Jimaixin™ electrophoretic profile presented slight changes compared with the original drug (first generation rEPO) and that a spike of Jimaixin™ in urine and serum was well identified by SDS-PAGE but with less performance by IEF-PAGE unless a neuraminidase treatment was applied first. The aims of this research were to perform an intravenous administration of Jimaixin™ on three healthy subjects (one microdose [10 IU/kg] and three therapeutic doses [50 IU/kg]) and to evaluate the detection in urine and blood up to 7 days post administration. Analysis of the samples showed that Jimaixin™ detection was complicated by IEF-PAGE due to the loss of the most distinctive basic isoforms. In addition, a neuraminidase treatment did not improve detection (contrary to the observations from spike experiments). On the contrary, Jimaixin™ was very efficiently detected in blood and urine by SDS-PAGE: up to 40 h after a microdose and up to 7 days after the therapeutic doses. The effect of Jimaixin™ on hematological parameters was limited to a clear but transitory increase of the reticulocytes. These data give new elements to better survey a potential misuse of Jimaixin™ by athletes.