Abstract
Ivosidenib is an approved drug for relapsed or refractory IDH1 mutant AML patients.
The goal of the present work is to develop and validate an LC-MS/MS method for the
quantitation of ivosidenib in mice dried blood spots (DBS) as per regulatory guideline
in the linearity range of 1.10–3293 ng/mL. To date there is no bioanalytical method
reported for quantitation of ivosidenib. The chromatographic resolution of ivosidenib
and internal standard (warfarin) was achieved on a C18 column with an isocratic mobile phase. All validation parameters met the acceptance
criteria. The intra- and inter-day precision was in the range of 2.79–10.5 and 5.76–9.02%,
respectively. Ivosidenib was stable for 3 freeze/thaw cycles, up to 7 days at room
temperature and for one month at −80°C. The applicability of the validated method
is shown in a mice pharmacokinetic study. Ivosidenib was quantifiable up to 24 and
36 h following intravenous and oral administration to mice, respectively. The oral
bioavailability was 48%. Comparison of DBS vs. plasma concentrations of ivosidenib
showed excellent correlation, indicating DBS can be used as an alternative for plasma
for pharmacokinetic analysis.
Key words
lvosidenib - dried blood spot - LC-MS/MS - method validation - mice blood - pharmacokinetics
