Determination of trimebutine and desmethyl-trimebutine in human plasma by HPLC.
A simple and sensitive HPLC method has been developed to measure trimebutine (CAS 39133-31-8, maleate: CAS 34140-59-5) and its main metabolite desmethyl-trimebutine in human plasma. The method was validated according to the Washington Consensus Conference on the Validation of Analytical Methods. It involved extraction of the plasma with n-hexane containing 2-pentanol, followed by reversed-phase HPLC using a Partisil ODS2 10 microns column and UV detection at 265 nm. The retention times of the internal standard (procaine), desmethyl-trimebutine and trimebutine were 2.4, 4.3 and 6.5 min, respectively. The standard curves were linear from 20 ng.ml-1 (limit of quantitation) to 5000 ng.ml-1 for both compounds. The coefficient of variation for all the criteria of validation were less than 15%. The extraction recoveries obtained for trimebutine and desmethyl-trimebutine were about 90%. Both compounds were very stable upon storage in plasma. The method was tested by measuring the plasma concentrations following oral administration to humans during a bioequivalence study and was shown suitable for pharmacokinetic studies.
Lavit
M
M
Laboratoire de Pharmacocinétique et de Toxicologie Clinique, Centre Hospitalier Universitaire, Toulouse, France.
Saivin
S
S
Boudra
H
H
Michel
F
F
Martin
A
A
Cahiez
G
G
Labaune
J P
JP
Chomard
J M
JM
Houin
G
G
D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005765:Gastrointestinal Agents / Q000097:blood*; D006801:Humans; D007202:Indicators and Reagents; D011786:Quality Control; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet; D013810:Therapeutic Equivalency; D014287:Trimebutine / Q000031:analogs & derivatives* / Q000097:blood
D005765:Gastrointestinal Agents; D007202:Indicators and Reagents; C053065:N-desmethyltrimebutine; D014287:Trimebutine