Simultaneous determination of ginkgo flavonoids and terpenoids in plasma: Ammonium formate in LC mobile phase enhancing electrospray ionization efficiency and capacity

Extracts from Ginkgo biloba leaves confer their therapeutic effects through the synergistic actions of flavonoid and terpenoid components. We herein describe the development of an LC-MS/MS-based method for simultaneous determination of flavonoids (quercetin, kaempferol, and isorhamnetin) and terpenoids (bilobalide, ginkgolides A, B, C, and J) in acid-hydrolyzed plasma by circumventing cross-interference between the flavonoids and terpenoids identified. Notably, inclusion of ammonium formate (0.2 mM) in the mobile phase generated beneficial LC-electrolyte effects, including increased ESI efficiency and capacity, with the result that the newly developed procedure exhibits the highest analytical performance reported to date for ginkgo-associated studies. The method yields high sensitivity, negligible matrix interference and cross-interference, wide linear dynamic ranges, high sample throughput, and quite small initial sample size. The assay utility to dog pharmacokinetic measurements of commercial ginkgo products yielded the most comprehensive data on systemic exposure to the ginkgo compounds to date. The newly developed multi-analyte procedure should be widely useful.