The pharmacokinetic (PK) and bioequivalence (BE) studies of
two formulations of azelastine (AZ) was carried out in 18 healthy male Korean
volunteers according to a randomized crossover-design and were performed by a
new validated liquid chromatography coupled to tandem mass spectrometry
(LCMS/MS) method for quantitative analysis of plasma AZ. Subjects were given
single dose of 2 tablets of 1 mg AZ of each formulation with 240 ml of water to
subjects on 2 treatment days separated by one week washout period. After
dosing, serial blood samples were collected for a period of 96 hours. AZ and
the clomipramine (IS) were separated using a mobile phase of acetonitrile-5 mM
NH4AC (8：2, v/v, pH=6.4) with flow rate of 0.25
ml/min over Luna C18 column. Analysis required 0.2 ml of plasma and involved a
solid extraction with an Oasis HLB cartridge by on-line clean-up extraction
automation system and then directly injected into HPLC with an API 3000 MS
system by multiple reactions monitoring (MRM) mode. Several PK parameters
(including AUC0-t, AUC0-infinity, Cmax, Tmax, T1/2 and Ke) were determined from
the plasma concentration of AZ of both formulations. The AUC and Cmax was
tested for BE after log-transformation of the data. The ionization was
optimized using ESI (+) and selectivity was achieved by MS-MS analysis, m/z 112.0
and m/z 86.1 for AZ and IS, respectively. The calibration curves with r2＞0.999
were linear over a working range of 20∼2000 pg/ml.
No endogenous compounds were found to interfere with the analysis. The inter-
and intra-day accuracy was in the ranges of 89.9∼109.3% and precision of inter- and intra-day expressed as relative
standard deviation were 2.73∼8.79 %. No
significant difference was found based on ANOVA; 90% confidance intervals
(91.77∼101.94% for AUC0-t; 90.44∼ 106.27% for AUC0-infinity; 92.22∼108.57% for
Cmax) for the test and reference drugs were found within FDA guideline of 80∼125%. Based on these statistical considerations, it was
concluded that test drug was bioequivalent to the reference drug and therefore,
may be interchangeably in the management of allergic or bronchial asthma and
prophylaxis of mucositis due to cancer chemoradiotherapy. This validated method
was found to be good performance on PK and BE studies for AZ. (Cancer Prev Res
12, 84-91, 2007).
Author (s) Details
Professor Ju-Seop Kang, Author (s) Details
Department of Pharmacology and Clinical Pharmacology Laboratory, College of Medicine, Hanyang University, Seoul 133-791, Korea.
View Book :- http://bp.bookpi.org/index.php/bpi/catalog/book/195
No comments:
Post a Comment