Chromatographic/Mass Spectrometric Method for the Estimation of Itraconazole and its Metabolite in Human Plasma

Abstract

A HPLC/mass spectrometry method for the estimation of itraconazole (CAS 84625-61-6, ITR) and its active metabolite hydroxyitraconazole (CAS 112559-91-8, HOX) in human plasma was developed. Terconazole (CAS 67915-31-5) was used as an internal standard. The analytical method was fully validated according to FDA and EMEA requirements. The accuracy and precision of the developed method was satisfactory and stability studies showed an acceptable variation (below 15%) of ITR and HOX concentrations when the samples were stored frozen at -75 degrees C for 95 days. The developed method was successfully used for a comparative 2 x 2 period, crossover bioequivalence study of two preparations of ITR (Itrakonazol Genexo 100 mg as the test drug) performed on 36 healthy volunteers.

Advanced In Vivo Prediction by Introducing Biphasic Dissolution Data into PBPK Models

“…Itraconazole exhibits a plasma protein binding of 99.8%. It is a substrate for CYP3A4 metabolism [ 38 ] and enters the enterohepatic circulation [ 39 ]. Itraconazole was intravenously administered as a β-cyclodextrin solution, which formed the basis of the distribution/elimination model [ 40 ].…”

Method of variability optimization in pharmacokinetic data analysis

“…Blood samples were collected just prior to administration and at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0, and 72.0 h after the administration. The concentration analyses were performed using tandem mass spectrometry, using the method described previously (Grabowski et al 2009). The study was approved by Independent Ethics Committee of District Council of Physicians, Baśniowa 3, Warsaw (Resolution No.…”