Quantitative determination of alpha-cyclodextrin in human plasma by liquid chromatography/positive ion electrospray mass spectrometry.
A sensitive and selective method for the determination of alpha-cyclodextrin in human plasma is described using beta-cyclodextrin as an internal standard. After protein precipitation with perchloric acid, the analytes were isolated from human plasma by solid-phase extraction on Bond Elut C18 cartridges. The compounds were chromatographed on a narrow-bore aminopropyl column (125 x 2 mm i.d., 5 microm) and analyzed by electrospray ionization mass spectrometry in the positive selected-ion mode using the [M+NH4]+ ion. The lower limit of quantitation was 5 ng ml(-1) of human plasma. Linear calibration curves were obtained over the concentration range 5-1000 ng ml(-1) of human plasma. The intra- and inter-assay precisions were <18% and the accuracy was <10.5% over the entire concentration range. During the method development, the ionization efficiencies of the analytes in plasma samples originating from different sources were examined to overcome the matrix effect problems caused by co-eluting endogenous compounds. The method was successfully applied to pharmacokinetic studies in human volunteers.
Hammes
W
W
Department of Bioanalytics, Schwarz Pharma AG, Monheim, Germany. wilhelm.hammes@schwarzpharma.com
Bourscheidt
C
C
Büchsler
U
U
Stodt
G
G
Bökens
H
H
D001774:Blood Chemical Analysis / Q000379:methods* / Q000592:standards / Q000706:statistics & numerical data; D002240:Carbohydrate Sequence; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000097:blood* / Q000737:chemistry / Q000592:standards; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods* / Q000592:standards / Q000706:statistics & numerical data; D008969:Molecular Sequence Data; D012015:Reference Standards; D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins; C031215:betadex; C032613:alpha-cyclodextrin