dc.contributor.author	Nwabufo, Chukwunonso
dc.contributor.author	El-Aneed, Anas
dc.contributor.author	Krol, Ed
dc.date.accessioned	2023-11-16T19:46:58Z
dc.date.available	2023-11-16T19:46:58Z
dc.date.issued	2019
dc.description.abstract	Rationale: Novel bifunctional compounds composed of a caffeine scaffold attached to nicotine (C8-6-N), 1-aminoindan (C8-6-I), or caffeine (C8-6-C8) were designed as therapeutics or diagnostics for Parkinson's disease (PD). In order to probe their pharmacological and toxicological profile, an appropriate analytical method is required. The goal of this study is to establish a tandem mass spectrometric fingerprint for the development of quantitative and qualitative methods that will aid future assessment of the in vitro and in vivo absorption, distribution, metabolism, excretion (ADME) and pharmacokinetic properties of these lead bifunctional compounds for PD. Methods: Accurate mass measurement was performed using a hybrid quadrupole orthogonal time-of-flight mass spectrometer while multistage MS/MS and MS3 analyses were conducted using a triple quadrupole linear ion trap mass spectrometer. Both instruments are equipped with an electrospray ionization (ESI) source and were operated in the positive ion mode. The source and compound parameters were optimized for all three tested bifunctional compounds. Results: The MS/MS analysis indicates that the fragmentation of C8-6-N and C8-6-I is driven by the dissociation of the nicotine and 1-aminoindan moieties, respectively, but not caffeine. A significant observation in the MS/MS fragmentation of C8-6-C8 suggests that a previously reported loss of acetaldehyde during caffeine dissociation is instead a loss of CO2. Conclusions: The collision-induced tandem mass spectrometry (CID-MS/MS) analysis of these novel bifunctional compounds revealed compound-specific diagnostic product ions and neutral losses for all three tested bifunctional compounds. The established MS/MS fingerprint will be applied to the future development of qualitative and quantitative methods.	en_US
dc.description.sponsorship	NSERC, CFI	en_US
dc.description.version	Peer Reviewed	en_US
dc.identifier.citation	Nwabufo CK, El-Aneed A, Krol ES. Tandem mass spectrometric analysis of novel caffeine scaffold-based bifunctional compounds for Parkinson's disease. Rapid Commun Mass Spectrom. 2019 Dec 15;33(23):1792-1803. doi: 10.1002/rcm.8540.	en_US
dc.identifier.doi	10.1002/rcm.8540
dc.identifier.uri	https://hdl.handle.net/10388/15254
dc.rights	Attribution-NonCommercial-ShareAlike 2.5 Canada	*
dc.rights.uri	http://creativecommons.org/licenses/by-nc-sa/2.5/ca/	*
dc.title	Tandem mass spectrometric analysis of novel caffeine scaffold-based bifunctional compounds for Parkinson's disease	en_US
dc.type	Postprint	en_US

Tandem mass spectrometric analysis of novel caffeine scaffold-based bifunctional compounds for Parkinson's disease

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