Determination of 2-hydroxypropyl-gamma-cyclodextrin in plasma of cynomolgus monkeys after oral administration by gas chromatography-mass spectrometry.
This report describes a specific and highly sensitive gas chromatography-mass spectrometry (GC-MS) assay for the analysis of industrially produced 2-hydroxypropyl-gamma-cyclodextrin, a heterogeneous mixture of homologues and isomers, in plasma of cynomolgus monkeys. Instead of analyzing the polysaccharide mixture as a whole, in a first step the HP-gamma-cyclodextrin mixture, together with the internal standard (2,6-di-O-methyl-beta-cyclodextrin), was deuteromethylated, and in a second step hydrolyzed with hydrochloric acid to the respective monosaccharides. The resulting reaction mixture was trimethylsilylated to 1,4-bis(O-trimethylsilyl)-2,3-bis-O-deuteromethyl-6-O-2'-deuter omethoxypropylglucose (representative for HP-gamma-CD) and 1,4-bis-(O-trimethylsilyl)-bis-2,6-O-methyl-3-O-deuteromethylglucose+ ++ (representative for the internal standard), respectively, and analyzed by GC-MS. The limit of quantification of this assay was 20 nmol/l.
Blum
W
W
Novartis Pharma AG, Research Department, Basel, Switzerland.
Aichholz
R
R
Ramstein
P
P
Fetz
A
A
Raschdorf
F
F
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000284:Administration, Oral; D000818:Animals; D002138:Calibration; D003505:Cyclodextrins / Q000008:administration & dosage / Q000097:blood*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D008252:Macaca fascicularis; D012015:Reference Standards; D015203:Reproducibility of Results; D047392:beta-Cyclodextrins; D047408:gamma-Cyclodextrins
D003505:Cyclodextrins; D047392:beta-Cyclodextrins; D047408:gamma-Cyclodextrins; C479659:hydroxypropyl-gamma-cyclodextrin; D000073738:2-Hydroxypropyl-beta-cyclodextrin