Stereoselective high-performance liquid chromatography determination of propranolol and 4-hydroxypropranolol in human plasma after pre-column derivatization.
A stereoselective reversed-phase HPLC assay to quantify S-(-) and R-(+) enantiomers of propranolol and 4-hydroxypropranolol in human plasma was developed. The method involved liquid-liquid extraction for sample clean-up and employed 2,3,4,6-tetra-O-acetyl-beta-glucopyranosyl isothiocyanate as a pre-column chiral derivatization reagent. The internal standard used was 4-methylpropranolol. The derivatized products were separated on an Altex C18 column using a mixture of acetonitrile-water-phosphoric acid-triethylamine (58:42:0.1:0.06 and 50:50:0.15:0.06, v/v, for propranolol and 4-hydroxypropranolol, respectively) as mobile phase. The detection of propranolol derivatives was made at lambda(ex)=280 nm and lambda(em)=325 nm, and the corresponding 325 and 400 nm were used for 4-hydroxypropranolol derivatives. The assay was linear from 1 to 100 ng/ml and from 2 to 50 ng/ml using 0.5 ml of human plasma for propranolol and 4-hydroxypropranolol enantiomers, respectively. The present assay is used to quantify the enantiomers of propranolol and 4-hydroxypropranolol, respectively, in human plasma for pharmacokinetic studies.
Wu
S T
ST
Drug Metabolism and Pharmacokinetics Section, The DuPont Merck Pharmaceutical Company, Newark, DE 19714, USA.
Chang
Y P
YP
Gee
W L
WL
Benet
L Z
LZ
Lin
E T
ET
D000319:Adrenergic beta-Antagonists / Q000097:blood* / Q000493:pharmacokinetics; D000959:Antihypertensive Agents / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D017879:Isothiocyanates; D011433:Propranolol / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D013237:Stereoisomerism
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D017879:Isothiocyanates; C041943:2,3,4,6-tetra-O-acetylglucopyranosylisothiocyanate; C001422:4-hydroxypropranolol; D011433:Propranolol