High sensitivity determination of the remoxipride hydroquinone metabolite NCQ-344 in plasma by coupled column reversed-phase liquid chromatography and electrochemical detection.
An HPLC method for the determination of NCQ-344, a remoxipride metabolite with a hydroquinone structure, in human plasma is described. Special precautions for the sampling were necessary as the compound rapidly decomposes. An efficient clean-up of the plasma samples was necessary to make use of the inherent sensitivity of the electrochemical detector. This was accomplished by a fast and simple liquid-liquid extraction at pH 7.05 combined with further cleaning on-line by using a short cyanopropyl column as the first column in a column switching system. A heart-cut from the cyanopropyl column containing the NCQ-344 fraction was then injected onto the analytical octadecyl silica column and NCQ-344 was detected at an oxidation potential of 0.70 V. The absolute recovery was > 95% and concentrations down to 0.10 nM could be determined with acceptable precision. The NCQ-344 levels in a limited number of samples from patients given remoxipride were found to be between 0.10 and 1 nM. The remoxipride concentrations in the same samples were 5,000-20,000 nM.
Nilsson
L B
LB
Department of Bioanalysis, Analytical and Pharmaceutical R&D, Astra Arcus AB, Södertälje, Sweden.
D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D018492:Dopamine Antagonists / Q000097:blood* / Q000627:therapeutic use; D004563:Electrochemistry; D006801:Humans; D006873:Hydroquinones / Q000097:blood*; D017330:Remoxipride / Q000031:analogs & derivatives* / Q000097:blood* / Q000627:therapeutic use; D015203:Reproducibility of Results; D012457:Salicylamides / Q000097:blood; D012680:Sensitivity and Specificity
D018492:Dopamine Antagonists; D006873:Hydroquinones; C112341:NCQ 344; D012457:Salicylamides; D017330:Remoxipride; C050313:FLA 797