The determination of gemini surfactants used as gene delivery agents in cellular matrix using validated tandem mass spectrometric method

El-Aneed, Anas

The determination of gemini surfactants used as gene delivery agents in cellular matrix using validated tandem mass spectrometric method

dc.contributor.author	El-Aneed, Anas
dc.date.accessioned	2019-09-16T17:21:34Z
dc.date.available	2019-09-16T17:21:34Z
dc.date.issued	2018-10-03
dc.description.abstract	A simple, reliable flow injection analysis (FIA)-tandem mass spectrometric (MS/MS) method was developed for the determination of gemini surfactants, designated as 16-3-16, 16(Py)-S-2-S-(Py)16 and 16-7N(GK)-16, as gene delivery agents in cellular matrix. 16-3-16 is a conventional gemini surfactant bearing two quaternary amines, linked by a 3-carbon spacer region, 16(Py)-S-2-S-(Py)16 contains two pyridinium head groups, while 16-7N(GK)-16 bears a glycine-lysine di-peptide in the space region. The method was fully validated according to USFDA guidelines. It is the first time that FIA-MS/MS method was developed for the quantification of gemini surfactants, belonging to different structural families. The method was superior to existing liquid chromatographic (LC)-MS/MS methods in terms of sensitivity and time of analysis. Positive electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode were used on a triple quadrupole-linear ion trap (4000 QTRAP®) instrument. Deuterated internal standards were used to correct for matrix effects and variations in ionization within the ESI source. Isotope dilution standard curves were established in cellular matrix, with a linear range of 10nM-1000nM for 16-3-16 and 16(Py)-S-2-S-(Py)16, and 20nM-2000nM for 16-7N(GK)-16. The precision, accuracy, recovery and stability were all within the acceptable ranges as per the USFDA guidelines. The method was successfully applied for the quantification of target gemini surfactants in the nuclear fraction of PAM 212 keratinocyte cells treated with nanoparticles, which varied significantly and may explain differences in the observed efficiency and/or toxicity of these gemini surfactants in gene delivery.	en_US
dc.description.sponsorship	Natural Sciences and Engineering Research Council of Canada (NSERC), Canada Foundation for Innovation (CFI) Leaders Opportunity Fund.	en_US
dc.description.version	Peer Reviewed	en_US
dc.identifier.citation	Wei, J., Badea, I., Leary, S.C., and El-Aneed, A. (2018) The determination of gemini surfactants used as gene delivery agents in cellular matrix using validated tandem mass spectrometric method. J Pharm Biomed Anal. 2019 Feb 5;164:164-172.	en_US
dc.identifier.doi	10.1016/j.jpba.2018.10.003
dc.identifier.pmid	30390558
dc.identifier.uri	http://hdl.handle.net/10388/12313
dc.language.iso	en	en_US
dc.publisher	Elsevier	en_US
dc.rights	Attribution-NonCommercial-NoDerivs 2.5 Canada	*
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/2.5/ca/	*
dc.subject	FIA-MS/MS, quantification, gemini surfactants, lipid-based gene delivery agents, cellular matrix	en_US
dc.title	The determination of gemini surfactants used as gene delivery agents in cellular matrix using validated tandem mass spectrometric method	en_US
dc.type	Postprint	en_US