title: An indirect (derivatization) and a direct HPLC method for the determination of the enantiomers of ketorolac in plasma.
abstract: 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).
authors.affiliation: Syntex (U.S.A.), Inc., Palo Alto, CA 94303, USA.
authors.forename: I
authors.initials: I
authors.lastname: Tsina
authors.forename: Y L
authors.initials: YL
authors.lastname: Tam
authors.forename: A
authors.initials: A
authors.lastname: Boyd
authors.forename: C
authors.initials: C
authors.lastname: Rocha
authors.forename: I
authors.initials: I
authors.lastname: Massey
authors.forename: T
authors.initials: T
authors.lastname: Tarnowski
mesh_terms: 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
chemical_list: D018712:Analgesics, Non-Narcotic; D009961:Orosomucoid; D014046:Tolmetin; D020910:Ketorolac