動注化学療法における pharmacokinetics と臨床

Interpretation of MS–MS spectra of small-molecule signal transduction inhibitors using accurate-m/z data and m/z-shifts with stable-isotope-labeled analogues and metabolites

A rapid, sensitive, and reliable liquid chromatography-tandem mass spectrometric method was developed to quantify ipatasertib in dog plasma The dog plasma sample was deproteinated by using acetonitrile with ulixertinib as an internal standard followed by separation on a Spursil C18 -EP column with a gradient mobile phase comprising 2 mM ammonium acetate containing 01% formic acid and acetonitrile Positive ion electrospray was used, and multiple reaction monitoring transitions were m/z 4582 > 3872 for ipatasertib and m/z 4331 > 2621 for the internal standard The developed method was validated with a linear range of 03-1500 ng/mL, and with correlation coefficient greater than 09989 The lower limit of quantification was 03 ng/mL The intra- and inter-day precision ranged from 358 to 1432%, whereas the intra- and inter-day accuracy was in the range of -250-1325% No carry-over and matrix effects were observed under the current conditions The extraction recovery was demonstrated to be greater than 8543% Ipatasertib was stable during the storage, processing, and determination The validated assay was further successfully applied to a pharmacokinetic study of ipatasertib in dogs after oral and intravenous administrations The bioavailability of ipatasertib was determined to be 193%

Pharmacokinetics and bioavailability of ipatasertib in dog plasma using LC/MS/MS.

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Pharmacokinetics and bioavailability of ipatasertib in dog plasma using LC/MS/MS.