MassChemSite for In-Depth Forced Degradation Analysis of PARP Inhibitors Olaparib, Rucaparib, and Niraparib.
Journal
ACS omega
ISSN: 2470-1343
Titre abrégé: ACS Omega
Pays: United States
ID NLM: 101691658
Informations de publication
Date de publication:
21 Feb 2023
21 Feb 2023
Historique:
received:
07
12
2022
accepted:
20
01
2023
entrez:
27
2
2023
pubmed:
28
2
2023
medline:
28
2
2023
Statut:
epublish
Résumé
Drugs must satisfy several protocols and tests before being approved for the market. Among them, forced degradation studies aim to evaluate drug stability under stressful conditions in order to predict the formation of harmful degradation products (DPs). Recent advances in LC-MS instrumentation have facilitated the structure elucidation of degradants, although a comprehensive data analysis still represents a bottle-neck due to the massive amount of data that can be easily generated. MassChemSite has been recently described as a promising informatics solution for LC-MS/MS and UV data analysis of forced degradation experiments and for the automated structural identification of DPs. Here, we applied MassChemSite to investigate the forced degradation of three poly(ADP-ribose) polymerase inhibitors (olaparib, rucaparib, and niraparib) under basic, acidic, neutral, and oxidative stress conditions. Samples were analyzed by UHPLC with online DAD coupled to high-resolution mass spectrometry. The kinetic evolution of the reactions and the influence of solvent on the degradation process were also assessed. Our investigation confirmed the formation of three DPs of olaparib and the wide degradation of the drug under the basic condition. Intriguingly, base-catalyzed hydrolysis of olaparib was greater when the content of aprotic-dipolar solvent in the mixture decreased. For the other two compounds, whose stability has been much less studied previously, six new degradants of rucaparib were identified under oxidative degradation, while niraparib emerged as stable under all stress conditions tested.
Identifiants
pubmed: 36844573
doi: 10.1021/acsomega.2c07815
pmc: PMC9948214
doi:
Types de publication
Journal Article
Langues
eng
Pagination
7005-7016Informations de copyright
© 2023 The Authors. Published by American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
Références
J Pharm Biomed Anal. 2002 Jun 15;28(6):1011-40
pubmed: 12049968
J Chem Inf Model. 2021 Jun 28;61(6):2706-2719
pubmed: 34061520
J Chem Inf Model. 2007 Nov-Dec;47(6):2172-81
pubmed: 17910431
Clin Cancer Res. 2017 Dec 1;23(23):7165-7170
pubmed: 28751443
Adv Drug Deliv Rev. 2007 Jan 10;59(1):29-37
pubmed: 17187892
Drugs. 2015 Feb;75(2):231-40
pubmed: 25616434
Int J Mol Sci. 2021 Apr 19;22(8):
pubmed: 33921561
Pest Manag Sci. 2020 Feb;76(2):721-729
pubmed: 31373749
J Pharm Biomed Anal. 2018 Oct 25;160:89-98
pubmed: 30075398
Molecules. 2019 Feb 27;24(5):
pubmed: 30818845
J Med Chem. 2008 Oct 23;51(20):6581-91
pubmed: 18800822
J Pharm Biomed Anal. 2022 Jun 5;215:114753
pubmed: 35447490
J Pharm Biomed Anal. 2008 Sep 29;48(2):247-53
pubmed: 18082992
Molecules. 2022 Mar 14;27(6):
pubmed: 35335245
Molecules. 2019 Oct 22;24(20):
pubmed: 31652589
J Pharm Anal. 2014 Jun;4(3):159-165
pubmed: 29403878
J Pharm Biomed Anal. 2019 Feb 20;165:399-409
pubmed: 30590338
J Mass Spectrom. 2018 Oct;53(10):963-975
pubmed: 29987857
Biomed Chromatogr. 2009 Apr;23(4):419-25
pubmed: 19016229
PDA J Pharm Sci Technol. 2014 5/6;68(3):221-238
pubmed: 25188345