Determination of epimers 22R and 22S of budesonide in human plasma by high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.
A highly sensitive and selective method has been developed for the simultaneous quantification of 22R- and 22S-epimers of budesonide in human plasma. The drug was isolated from human plasma using C18 solid-phase extraction cartridges and was acetylated with a mixture of 12.5% acetic anhydride and 12.5% triethylamine in acetonitrile to form the 21-acetyl derivatives. Deuterium-labelled budesonide was synthesized and determined to have an isotopic purity > 99%. This was used as the internal standard. Epimers were quantified by automated liquid chromatography-atmospheric pressure chemical ionization mass spectrometry, operating in selected ion mode at m/z 473.2 and m/z 476.2. Linear responses were observed for both epimers over the range 0.25 to 10.0 ng/ml. The average recoveries of 22R- and 22S-epimers of budesonide from human plasma were 87.4% and 87.0%, respectively. The lower limit of quantification for each epimer was 0.25 ng/ml, corresponding to 50.0 pg of analyte on column. Within- and between-day coefficients of variation were 8.6% and 4.0%, respectively.
Li
Y N
YN
Department of Pharmacy, University of Sydney, NSW, Australia.
Tattam
B
B
Brown
K F
KF
Seale
J P
JP
D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000032:analysis / Q000097:blood* / Q000737:chemistry; D001274:Atmospheric Pressure; D019819:Budesonide; D002851:Chromatography, High Pressure Liquid; D002940:Circadian Rhythm; D005938:Glucocorticoids; D006801:Humans; D016014:Linear Models; D013058:Mass Spectrometry; D011282:Pregnenediones / Q000032:analysis / Q000097:blood* / Q000737:chemistry; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D014316:Tritium
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D011282:Pregnenediones; D014316:Tritium; D019819:Budesonide