DEVELOPMENT AND APPLICATION OF A GAS-CHROMATOGRAPHIC MASS-SPECTROMETRIC MASS-SPECTROMETRIC METHOD FOR THE DETERMINATION OF 5-METHOXYFLAVONEIN RAT AND DOG PLASMA

A gas chromatographic/mass spectrometric/mass spectrometric method was developed for the determination of 5-methoxyflavone in plasma. Optimi zed detection schemes for 5-methoxyflavone readily allow a limit of qu antification of 1 ng ml(-1) in rat or dog plasma (1.0 ml sample volume ). The complete analysis time (injection to injection) is less than 9 min and allows for rapid automated sample throughput. Additional advan tages include a high degree of specifity and good accuracy and precisi on. This type of rapid tandem mass spectrometric assay has been found to be particularly useful in pharmaceutical discovery, since an assay for one compound can be quickly developed, utilized and then modified to determine analogs of similar structure, Application of this methodo logy to pilot preclinical pharmacokinetic studies of the drug indicate d that it is rapidly absorbed and cleared, with an apparent terminal h alf-life of about 15 min in dogs, Bioavailability in the two dogs test ed ranged 33 to 72%, but was about 25% in rats.