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-ma ss spectrometry (GC-MS) assay for the analysis of industrially produced 2-h ydroxypropyl-gamma-cyclodextrin, a heterogeneous mixture of homologues and isomers, in plasma of cynomolgus monkeys. Instead of analyzing the polysacc haride mixture as a whole, in a first step the HP-gamma-cyclodextrin mixtur e, together with the internal standard (2,6-di-O-methyl-beta-cyclodextrin), was deuteromethylated, and in a second step hydrolyzed with hydrochloric a cid to the respective monosaccharides. The resulting reaction mixture was t rimethylsilylated to 1,4-bis(O-trimethylsilyl)-2,3-bis-O-deuteromethyl-6-O2 '-deutromethoxypropylglucose (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. (C) 1998 Elsevier Science B .V. All rights reserved.