Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10553641 | Journal of Pharmaceutical and Biomedical Analysis | 2009 | 6 Pages |
Abstract
A chiral HPLC method was validated and successfully applied for the determination of formoterol stereoisomers and their inversion products in an aqueous matrix stored at 5-70 °C up to 3 weeks. Analysis was performed on a Chiral-AGP column (100 Ã 4-mm, 5-μm) using a variable mixture of mobile phase A (50-mM sodium phosphate buffer, pH 7.0) and B (10% v/v IPA) at a flow rate of 1.3 ml minâ1, and UV detection at 242 nm. All four formoterol stereoisomers were adequately resolved with acceptable detection and quantitation limits varying from 0.01-0.04 μg/ml and 0.04-0.1 μg/ml, respectively. The method showed acceptable accuracy (â¥88%), precision (RSD â¤Â 8.5%) and good linearity (r2 â¥Â 0.9999) over the concentration range investigated. While interconversion at 5 ± 3 °C and 25 ± 2 °C/60% RH ±5% RH was too low to be determined accurately within the study period, chiral inversion of formoterol stereoisomers measured at high temperatures followed the first order rate kinetics and occurred at a single chiral center, resulting in the reversible formation of diastereoisomers, (R,R) â (S,R) and (S,S) â (R,S). No enantiomerization or diastereomerization occurred. There was no significant difference in inversion of the active components in racemic (R,R/S,S)-formoterol fumarate and the single isomer (R,R)-arformoterol tartrate drug formulations, and both drugs are expected to maintain their stereochemical integrity throughout the proposed shelf-life at the recommended storage condition (5 ± 3 °C).
Related Topics
Physical Sciences and Engineering
Chemistry
Analytical Chemistry
Authors
Samuel Akapo, Chithra McCrea, June Gupta, Mark Roach, Wayne Skinner,