Sensitive fused-silica capillary gas chromatographic assay using electron-capture detection for indomethacin in ovine fetal fluids.
A sensitive gas chromatographic (GC) method with electron-capture detection (ECD) has been developed to quantitate indomethacin (IND) in plasma, urine, amniotic, and tracheal fluids obtained from the pregnant sheep model. IND and the internal standard, alpha-methylindomethacin (alpha-Me-IND) are extracted by a simple liquid-liquid extraction procedure using ethyl acetate and derivatized with N-methyl-N-(tert.-butyldimethyl-silyl)trifluoroacetamide (MTBSTFA) at 60 degrees C for 50 min. The limit of quantitation (LOQ) is 1 ng/ml with a C.V. < 10% and signal-to-noise ratio > 10. Recoveries from all fluids were greater than 80%. Calibration curves were linear over the range of 1-32 ng/ml with a coefficient of determination (r2) > 0.999. Inter- and intra-day coefficients of variation were < 10% at concentrations of 2-32 ng/ml, and < 20% at the LOQ. Applicability of the developed method is demonstrated for a pharmacokinetic study of IND samples collected following long-term infusion of IND in a chronically instrumented ovine fetus.
Krishna
R
R
Division of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Riggs
K W
KW
Walker
M P
MP
Kwan
E
E
Rurak
D W
DW
D000081:Acetamides; D000653:Amniotic Fluid / Q000737:chemistry; D000818:Animals; D001826:Body Fluids / Q000737:chemistry*; D002138:Calibration; D002849:Chromatography, Gas; D005312:Fetal Blood / Q000737:chemistry; D005333:Fetus / Q000737:chemistry*; D005463:Fluoroacetates; D007213:Indomethacin / Q000031:analogs & derivatives / Q000032:analysis* / Q000097:blood / Q000652:urine; D013058:Mass Spectrometry; D017646:Organosilicon Compounds; D012015:Reference Standards; D012756:Sheep
D000081:Acetamides; D005463:Fluoroacetates; D017646:Organosilicon Compounds; C059151:N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide; D007213:Indomethacin