Implication of free cholesterol in LC-MS response enhancement.
BACKGROUND
In the context of matrix effects in bioanalytical LC-MS/MS, a speculative link between free cholesterol, the recoveries of the compound from three common extraction procedures, and response enhancement was qualitatively investigated.


RESULTS
Injections on-column of cholesterol both in solution and extracts, in conjunction with post-column infusion of three representative drugs, reveal a direct role in pronounced response enhancement for two out of three analytes, under one set of LC-MS/MS conditions, for the majority of typical plasma extraction procedures, where electrospray-based gaseous ion generation is used.


CONCLUSIONS
Cholesterol has been shown to have a strong association with LC-MS/MS response enhancement and ideally should be monitored during method development, reinforcing the reasoning behind minimizing SPE elution volumes and avoiding less selective means of sample preparation.
Department of Bioanalytical Services, Huntingdon Life Sciences, Mettlers Road, East Millstone, NJ 08875-2360, USA. macneillr@princeton.huntingdon.com
Robert
R
MacNeill
Amy
A
Farside
Vishva
V
Acharya
Ryan
R
Stromeyer
Bryan
B
Urbanowicz
Marc
M
Moussallie
D000818:Animals; D002784:Cholesterol / Q000032:analysis* / Q000737:chemistry*; D002853:Chromatography, Liquid / Q000379:methods*; D003511:Cyclohexanols / Q000097:blood / Q000737:chemistry; D006801:Humans; D007654:Ketoconazole / Q000097:blood / Q000737:chemistry; D059625:Liquid-Liquid Extraction; D004364:Pharmaceutical Preparations / Q000097:blood / Q000737:chemistry; D010949:Plasma / Q000737:chemistry; D051381:Rats; D052616:Solid Phase Extraction / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014230:Triazoles / Q000097:blood / Q000737:chemistry; D014363:Tryptamines / Q000097:blood / Q000737:chemistry; D000069470:Venlafaxine Hydrochloride
D003511:Cyclohexanols; D004364:Pharmaceutical Preparations; D014230:Triazoles; D014363:Tryptamines; C093622:rizatriptan; D000069470:Venlafaxine Hydrochloride; D002784:Cholesterol; D007654:Ketoconazole