Identification and structural elucidation of a new cetrorelix methylene dimer impurity in cetrorelix acetate by using LC-MS/MS

Copyright © 2021. Published by Elsevier B.V..

Cetrorelix, a potent third generation of luteinizing hormone releasing hormone (LHRH) antagonist, is a synthetic decapeptide used for treatment of infertility, prostatic hypertrophy and sexual hormone-dependent tumors. The approved drug of cetrorelix (Cetrotide, Asta Medica AG, Frankfurt, Germany.), was used for prevention of premature ovulation in patients undergoing a controlled ovarian stimulation (COS), followed by oocyte pick-up and assisted reproductive techniques, and has been shown safe and effective in controlled ovarian stimulation. Nevertheless, the study of aggregation products of cetrorelix was rarely reported. A simple liquid chromatography mass spectrometry (LC-MS/MS) method was developed for separation, identification and characterization of a new cetrorelix methylene dimer impurity in cetrorelix. The chromatographic separation was achieved on an XSelect Peptide CSH ™C18 column (150 × 4.6 mm, 3.5 μm particle size) using gradient elution with a mobile phase of ammonium formate buffer (pH 3.0, 20 mM), acetonitrile at a flow rate 1.0 mL min-1, and an ultraviolet detection wavelength of 226 nm. The new cetrorelix methylene dimer impurity was characterized by LC-MS/MS and it characteristic fragment ions were summarized. A simple, fast and accurate method was established for the determination of the molecular weight and structure of the new cetrorelix methylene dimer impurity. In this study, the results showed that the cetrorelix was highly unstable in formaldehyde conditions. In addition, it is proposed that the impact of formaldehyde in the environment on the quality of cetrorelix acetate for Injection should be evaluated during the production process.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:197

Enthalten in:

Journal of pharmaceutical and biomedical analysis - 197(2021) vom: 15. Apr., Seite 113946

Sprache:

Englisch

Beteiligte Personen:

Li, Mingliang [VerfasserIn]
Li, Huapeng [VerfasserIn]
Huang, Heqing [VerfasserIn]
Li, Yanzhi [VerfasserIn]
Qin, Li [VerfasserIn]
Xu, Xuan [VerfasserIn]
Zheng, Qiang [VerfasserIn]
Wang, Donghai [VerfasserIn]
Zhang, Minghui [VerfasserIn]
Sun, Yanhua [VerfasserIn]
Yang, Qingmin [VerfasserIn]

Links:

Volltext

Themen:

33515-09-2
Cetrorelix
Cetrorelix methylene dimer
Gonadotropin-Releasing Hormone
Journal Article
LC–MS/MS
OON1HFZ4BA

Anmerkungen:

Date Completed 17.06.2021

Date Revised 17.06.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.jpba.2021.113946

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM321697693