Determination of the enantiomeric composition of a new insulin sensitizer in plasma samples from non-clinical and clinical investigations using chiral HPLC with electrospray tandem mass spectrometric detection.
Two drug assays were developed and applied to assess the enantiomeric composition of an insulin sensitizer drug in plasma after administration of its racemate to man, and in human and animal plasma and serum samples generated after in vitro experiments. The sample preparation for the assays consisted either of protein precipitation and column-switching, or liquid-liquid extraction and direct injection. Subsequently, both assays employed chiral HPLC coupled to atmospheric pressure ionization mass spectrometry. An interconversion of the racemate to a mixture enriched with the (+)-enantiomer could be confirmed for all species and biological matrices. The individual enantiomers could be quantified in the concentration range 0.5-500 ng/ml, starting with a 100-microl plasma aliquot. Inter- and intra-assay precision and accuracy were in the range 0.1-7.9 and 88.8-106.0%, respectively. Run times of 5 min for a single sample allows the analysis of more than 200 samples overnight.
Lausecker
B
B
F. Hoffmann-La Roche Ltd., Pharmaceuticals Division, Non-Clinical Drug Safety, P.O. Box, CH-4070 Basel, Switzerland. berthold.lausecker@roche.com
Fischer
G
G
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000737:chemistry*; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013237:Stereoisomerism; D013844:Thiazoles / Q000097:blood / Q000737:chemistry*; D045162:Thiazolidinediones; D013876:Thiophenes / Q000097:blood / Q000737:chemistry*
C511003:5-((4-(2-(5-methyl-2-phenyl-oxazol-4-yl)ethoxy)benzo(2) thiophen-7-yl)methyl)-thiazolidine-2,4-dione; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D013876:Thiophenes