Chiral analysis of drug substance in clinical plasma extracts using achiral HPLC with circular dichroism detection.
A circular dichroism (CD) detector in series with a UV detector was used with reversed-phase gradient HPLC to do the chiral analysis of unresolved enantiomers of a single stereoisomer drug substance in extracts of clinical plasma samples. The CD/UV peak area ratio of the unresolved enantiomers in the plasma extracts was calculated and compared with pure drug substance standards to show that there was no racemization of the chiral center during pharmacokinetic studies. The CD detector can be used only with chiral compounds with a UV chromophore and the limit of detection was approximately 5 ng with the drug substance and chromatographic conditions used in this study.
Williams
R C
RC
Pharmaceutical R&D, DuPont Pharmaceuticals Co., Wilmington, DE 19880-0353, USA. reed.c.williams@dupontpharma.com
Edwards
J F
JF
Joshi
A S
AS
Aubry
A F
AF
D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D006801:Humans; D011799:Quinazolines / Q000097:blood*; D052999:Quinazolinones; D013237:Stereoisomerism; D014466:Ultraviolet Rays
C413505:DPC 961; D011799:Quinazolines; D052999:Quinazolinones