MSⁿ, LC‐MS‐TOF and LC‐PDA studies for identification of new degradation impurities of bupropion

Abstract

Three new degradation impurities of bupropion were characterized through high performance liquid chromatography coupled to photodiode array detection and to time-of-flight mass spectrometry. Bupropion was subjected to the ICH prescribed stress conditions. It degraded to seven impurities (I-VII) in alkaline hydrolytic conditions which were optimally resolved on an XTerra C18 column (250 × 4.6 mm, 5 µm) with a ternary mobile phase comprising ammonium formate (20 mm, pH 4.0), methanol and acetonitrile (75:10:15, v/v). The degradation impurities (III-V and VII) were characterized on the basis of mass fragmentation pattern of drug, accurate mass spectral and photodiode array data of the drug and degradation impurities. Compound V was found to be a known degradation impurity [1-hydroxy-1-(3-chlorophenyl)propan-2-one], whereas III, IV and VII were characterized as 2-hydroxy-2-(3'-chlorophenyl)-3,5,5-trimethylmorpholine, (2,4,4-trimethyl-1,3-oxazolidin-2-yl)(3-chlorophenyl)-methanone and 2-(3'-chlorophenyl)-3,5,5-trimethylmorphol-2-ene, respectively. Compound III was a known metabolite of the drug. This additional information on the degradation impurities can help in the development of a new stability-indicating assay method to monitor the stability of the drug product during its shelf-life as well as in development of a drug product with increased shelf-life.

Studies on photodegradation process of psychotropic drugs: a review

“…Antidepressant agents that can be considered as photostable are desipramine (ICH conditions) (Thiyagarajan et al 2008 ), citalopram (ICH conditions and UV radiation) (Sharma et al 2011 ; Tapkir et al 2016 ), escitalopram (wavelength 265 nm) (Kakde et al 2013 ), sertraline (UV-C) (Walash et al 2011b ), agomelatine (also UV-C) (El-Shaheny 2014 ), moclobemide (Patel et al 2008 ), and paroxetine (Venkatachalam and Chatterjee 2007 ) (sunlight in both cases). Bupropion (Bansal et al 2013 ) and dosulepin (Reddy et al 2014 ) are unstable under ICH conditions. Photostability of maprotiline was investigated under doubled ICH conditions (400 W m −2 and 2.4 * 10 6 lx h, the drug was unstable) (Đurić et al 2015 ).…”

“…However, simultaneous application of radiation and a basic environment lead to formation of five photoproducts. Structures of two of them were elucidated by Bansal et al ( 2013 ) (Fig. 17 ).…”

“… HPLC–MS None 2 identified (Kwon and Armbrust 2004 ) MetOH Natural sunlight HPTLC None None (photostable) (Venkatachalam and Chatterjee 2007 ) Sertraline MetOH Direct sunlight HPTLC None 1 detected (Hussain et al 2013 ) MetOH 245 nm Spectroph. Spectrofluorimetric None None (photostable) (Walash et al 2011a , b ) Bupropion Water–MetOH; HCl; NaOH N/A HPLC–PDA HPLC–MS None 5 (2 identified) (Bansal et al 2013 ) Moclobemide MetOH UV-C Spectroph. HPLC–MS None 3 identified (Skibiński and Komsta 2012 ) MetOH Natural sunlight HPTLC None None (photostable) (Patel et al 2008 ) Dosulepin SS N/A HPLC None None (Reddy et al 2014 ) Tianeptine SS UV-C TLC HPLC GC–MS None 4 detected (Khedr 2007 ) Duloxetine MetOH; SS Natural sunlight; UV HPLC None 4 detected (Patel et al 2010 ) ACN UV-C HPLC None 4 detected …”

Light-sensitive medicinal compounds – the actual review of studies and strategies in proceedings

“…Połączenie dwóch technik, takich jak chromatografia cieczowa -spektrometria mas (LC-MS) oraz chromatografia cieczowa -spektrometria magnetycznego rezonansu jądrowego (LC-NMR) są technikami obecnie często stosowanymi w celu identyfikacji produktów rozpadu substancji leczniczych. Co istotne, pozwalają one wyjaśnić strukturę produktów degradacji, a to z kolei pomaga podjąć niezbędne środki ostrożności, aby zahamować proces ich powstawania, a także utrzymać poziom zanieczyszczeń poniżej dopuszczalnych limitów i ograniczyć tworzenie się innych niepożądanych związków [39].…”

Determination of Bupropion and Its Impurities via a Chaotropic Chromatography Method Following Analytical Quality-by-Design Principles for Method Development

“…Several HPLC-UV [ 3 , 4 , 5 , 6 ] and HPLC-MS [ 7 , 8 , 9 , 10 ] methods have been reported for the determination of BUP and its major metabolites in biological fluids. Furthermore, the stability of BUP has been studied revealing four degradation impurities in alkaline pH [ 11 ], whereas three new impurities have been identified based on an LC-MS method [ 12 ]. A literature survey revealed a single HPLC method for the separation and determination of one related impurity and two alkaline degradants [ 13 ].…”