Identification and characterization of forced degradation products of vortioxetine by LC/MS/MS and NMR

被引：11

作者：

Ragi, Nagarjuna Chary ^{[1
,2
]}

Velma, Ganga Reddy ^{[3
]}

Pallerla, Pavan Kumar ^{[1
,2
]}

Siddiqua, Sana ^{[2
]}

Alugonda, Veeresham ^{[2
]}

Rachamalla, Hari Krishna Reddy ^{[1
,2
]}

Pabbaraja, Srihari ^{[3
]}

Sripadi, Prabhakar ^{[1
,2
]}

机构：

[1] Acad Sci & Innovat Res, New Delhi 110001, India

[2] CSIR, Ctr Mass Spectrometry, Dept Analyt & Struct Chem, Indian Inst Chem Technol, Hyderabad 500007, Telangana, India

[3] CSIR, Dept Organ Synth & Proc Chem, Indian Inst Chem Technol, Hyderabad 500007, India

来源：

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS | 2020年 / 188卷

关键词：

Vortioxetine; Stress degradation; Degradation products; High-resolution mass spectrometry; LC/MS/MS; IMPURITIES; TRENDS; SAFETY;

D O I：

10.1016/j.jpba.2020.113442

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

Vortioxetine (VTX) is a novel multimodal antidepressant drug that affects the serotoninergic and noradrenergic systems. In this work, the forced degradation of VTX was studied according to (ICH) Q1A (R2) guidelines. The study revealed that VTX was stable under thermal stress conditions and hydrolytic stress conditions i.e., acidic, basic and neutral conditions. In contrast, six degradation products (DPs) were formed under photolytic and oxidative stress conditions. The DPs were identified and characterized by high-resolution LC/MS and LC/MS/MS. The structures of major DPs were further confirmed by the synthesis and characterization by H-1 and C-13 NMR data. A possible mechanism for the formation of the VTX DPs via photolytic/oxidative stress degradation pathway was proposed. (C) 2020 Elsevier B.V. All rights reserved.

引用

页数：11

共 18 条

[1] Recent Trends in Product Development and Regulatory Issues on Impurities in Active Pharmaceutical Ingredient (API) and Drug Products. Part 2: Safety Considerations of Impurities in Pharmaceutical Products and Surveying the Impurity Landscape [J].

Alsante, Karen M. ;

Huynh-Ba, Kim C. ;

Baertschi, Steven W. ;

Reed, Robert A. ;

Landis, Margaret S. ;

Furness, Scott ;

Olsen, Bernard ;

Mowery, Mark ;

Russo, Karen ;

Iser, Robert ;

Stephenson, Gregory A. ;

Jansen, Patrick .

AAPS PHARMSCITECH, 2014, 15 (01) :237-251

[2]

[Anonymous], 2015, PHARMACOLOGY, DOI DOI 10.1016/J.PHARMTHERA.2014.07.001

[3]

[Anonymous], 2017, ACTA CHROMATOGR, DOI DOI 10.1556/1326.2017.29.3.02

[4]

[Anonymous], 2003, ICH GUID Q1A R2 STAB

[5] Discovery of 1-[2-(2,4-Dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): A Novel Multimodal Compound for the Treatment of Major Depressive Disorder [J].

Bang-Andersen, Benny ;

Ruhland, Thomas ;

Jorgensen, Morten ;

Smith, Garrick ;

Frederiksen, Kristen ;

Jensen, Klaus Gjervig ;

Zhong, Huailing ;

Nielsen, Soren Moller ;

Hogg, Sandra ;

Mork, Arne ;

Stensbol, Tine Bryan .

JOURNAL OF MEDICINAL CHEMISTRY, 2011, 54 (09) :3206-3221

[6]

Brummer H., 2011, LIFE SCI TECH B, V31

[7]

D'Agostino Andrew, 2015, P T, V40, P36

[8] Determination of vortioxetine and its degradation product in bulk and tablets, by LC-DAD and MS/MS methods [J].

de Diego, Marta ;

Correa, Diana ;

Mennickent, Sigrid ;

Godoy, Ricardo ;

Vergara, Carola .

BIOMEDICAL CHROMATOGRAPHY, 2018, 32 (11)

[9] A review of the clinical efficacy, safety and tolerability of the antidepressants vilazodone, levomilnacipran and vortioxetine [J].

Deardorff, William James ;

Grossberg, George T. .

EXPERT OPINION ON PHARMACOTHERAPY, 2014, 15 (17) :2525-2542

[10] FANCONI SYNDROME (ADULT TYPE) DEVELOPING SECONDARY TO INGESTION OF OUTDATED TETRACYCLINE [J].

GROSS, JM .

ANNALS OF INTERNAL MEDICINE, 1963, 58 (03) :523-+

← 1 2 →