Stereoselective high-performance liquid chromatographic assay of (+/-)-delmopinol in plasma using solid-phase extraction, a chiral derivatizing agent and electrochemical detection.
An enantioselective HPLC bioanalytical method for (+/-)-delmopinol was established in order to elucidate the pharmacokinetic behaviour of this chiral drug. (+/-)-Delmopinol and (+/-)-M1652, a structurally related compound used as internal standard, were extracted from plasma by a solid-phase extraction procedure using CN cartridges. The enantiomers were derivatized with a chiral derivatizing agent (R,R)-O,O'-di-p-toluoyl tartaric acid anhydride yielding diastereomeric derivatives which were separated on a reversed-phase column with acetonitrile-0.1 M ammonium acetate buffer (65:35, v/v) pH 5.7 as mobile phase. The resolution values of the diastereomeric derivatives of (-)- and (+)-M1652 and of the derivatives of (-)- and (+)-delmopinol were 1.03 and 1.46, respectively. The limit of quantitation was approximately 3 pmol (1 ng)/enantiomer per 0.5 ml plasma using electrochemical detection (+0.75 V versus Pd/PdO reference electrode). The effectiveness of the derivatization was > 98% and the total recovery of (+/-)-delmopinol and of (+/-)-M1652 from plasma or serum was found to be approximately 50%. The assay was applied to enantioselective pharmacokinetic investigations in humans, rats and dogs but showing here only one concentration time curve of the (+)- and (-)-delmopinol in a human subject after administering (+/-)-delmopinol in form of an aqueous mouth wash solution for 60 s.
Egginger
G
G
Institute of Pharmaceutical Chemistry, Karl-Franzens-University of Graz, Austria.
Blaschke
E
E
Lindner
W
W
Olsson
A M
AM
D000812:Anhydrides; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D004285:Dogs; D006801:Humans; D009025:Morpholines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D013644:Tartrates
D000812:Anhydrides; D009025:Morpholines; C087674:O,O'-di-4-toluoyl tartaric acid anhydride; D013644:Tartrates; C073738:delmopinol