title: Liquid chromatography/atmospheric pressure chemical ionization ion trap mass spectrometry of bilobalide in plasma and brain of rats after oral administration of its phospholipidic complex.
abstract: Standardized extracts of Ginkgo biloba L. leaves are widely used in clinical practice for the symptomatic treatment of mild to moderate dementia syndromes, cerebral insufficiency and for the enhancement of cognitive function. The main active components present in G. biloba extracts are flavonol-glycosides and terpene-lactones. In recent investigations, the sesquiterpene trilactone bilobalide has been described to exert an interesting neuroprotective effect when administered systemically to experimental animals. Oral administration of terpene-lactones either as standardized extracts or purified products is characterized by a low bioavailability. While preparing phospholipidic complex of G. biloba extracts or bilobalide, plasma levels of terpenes and sesquiterpene increase. In the present study, phospholipidic complex of bilobalide (IDN 5604) has been administered orally to rats and bilobalide levels have been determined in plasma and brain by means of a validated method based on liquid chromatography coupled to atmospheric pressure chemical ionization ion trap mass spectrometry (LC/APCI-ITMS). Due to its sensitivity (about 3pmol/ml) and specificity, LC/APCI-ITMS method proved to be a very powerful tool for pharmacokinetic studies of Ginkgo terpene-lactones. The results of the present study clearly confirm the improvement of oral bioavailability of bilobalide administered as phospholipidic complex and, for the first time, demonstrate the detection of significative amounts of bilobalide in brain. This last finding agrees with the neuroprotective activity observed for bilobalide.
authors.affiliation: Institute for Biomedical Technologies, Proteomics and Metabolomics Unit - CNR, Via Fratelli Cervi, 93, 20090 Segrate, Milan, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Rossi
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Basilico
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rossoni
authors.forename: Antonella
authors.initials: A
authors.lastname: Riva
authors.forename: Paolo
authors.initials: P
authors.lastname: Morazzoni
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Mauri
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001274:Atmospheric Pressure; D001682:Biological Availability; D001921:Brain / Q000378:metabolism*; D002138:Calibration; D003517:Cyclopentanes / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D005663:Furans / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D046934:Ginkgolides / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D010743:Phospholipids / Q000008:administration & dosage*; D051381:Rats; D012015:Reference Standards
chemical_list: D003517:Cyclopentanes; D005663:Furans; D046934:Ginkgolides; D010743:Phospholipids; C073710:bilobalide