An indirect (derivatization) and a direct HPLC method for the determination of the enantiomers of ketorolac in plasma.
An indirect and a direct HPLC method for the quantification of the (R) and (S) enantiomers of ketorolac are described here. The indirect method employs the chiral amine (+)-R-1-(1-naphthyl)ethylamine to form disastereomeric amides; separation of the disastereomeric derivates is achieved by normal-phase HPLC with a mobile phase of ethyl acetate-hexane. The direct method uses a C18 solid-phase extraction column to extract ketorolac enantiomers from plasma; the reconstituted extract is then injected onto an alpha 1-acid glycoprotein chiral column using a mobile phase of isopropanol-phosphate buffer (0.05 M; pH 5.5). Both methods are reproducible, accurate, and stereospecific, and both have equivalent quantification limits (0.02 microgram ml-1 of plasma for each enantiomer), ranges (0.02-2.0 micrograms per aliquot of plasma), precision (% relative standard deviations of < or = 10.5% and < or = 10.8% for (R)- and (S)-ketorolac respectively), and accuracy (mean recoveries of 88.4-110% and 90.1-110% for (R)- and (S)-ketorolac respectively). Results of analyses of clinical samples by the two methods showed excellent agreement (slope near 1.0 and coefficients of correlation between 0.9740 and 0.9864 for both enantiomers).
Tsina
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Syntex (U.S.A.), Inc., Palo Alto, CA 94303, USA.
Tam
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YL
Boyd
A
A
Rocha
C
C
Massey
I
I
Tarnowski
T
T
D018712:Analgesics, Non-Narcotic / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004355:Drug Stability; D005069:Evaluation Studies as Topic; D006801:Humans; D020910:Ketorolac; D009961:Orosomucoid; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D014046:Tolmetin / Q000031:analogs & derivatives* / Q000097:blood
D018712:Analgesics, Non-Narcotic; D009961:Orosomucoid; D014046:Tolmetin; D020910:Ketorolac