title: Liquid chromatography-electrospray mass spectrometry determination of free and total concentrations of ropivacaine in human plasma.
abstract: A specific and sensitive liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method was developed for the determination of free and total ropivacaine in human plasma. The work-up procedure involved a simple precipitation of plasma proteins with methanol. Etidocaine served as the internal standard. After microscale equilibrium-dialysis, measurement of free ropivacaine levels was performed after direct injection of the dialysate into the chromatograph. The system used a Zorbax eclipse XD8 C8 analytical column packed with 5 microm diameter particles as the stationary phase. The mobile phase consisted of a 15-min gradient (mobile phase A: 0.05% (v/v) trimethylamine in acetonitrile, mobile phase B: 2mM ammonium formate buffer (pH 3)). Mass spectrometric data were acquired in single ion monitoring mode at m/z 275 for ropivacaine and m/z 277 for etidocaine. The drug/internal standard peak area ratios (plasma) or peak areas (dialysate) were linked via a quadratic relationship to concentrations. Precision ranged from 1 to 7.6% accuracy was between 92.6 and 109%. The lower limits of quantitation were 1 microg/l in plasma and 2 microg/l in the dialysate. This method was found suitable for the analysis of plasma samples collected during a clinical trial performed in 30 infants undergoing epidural anaesthesia or continuous psoas compartment block.
authors.affiliation: Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital, Montpellier, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Mathieu
authors.forename: Dominique
authors.initials: D
authors.lastname: Hillaire-Buys
authors.forename: Christophe
authors.initials: C
authors.lastname: Dadure
authors.forename: Franck
authors.initials: F
authors.lastname: Barnay
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Mathieu-Daudé
authors.forename: Françoise
authors.initials: F
authors.lastname: Bressolle
mesh_terms: D000577:Amides / Q000097:blood*; D000772:Anesthesia, Local / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods*; D003956:Dialysis; D004355:Drug Stability; D005041:Etidocaine; D006801:Humans; D009407:Nerve Block; D016658:Psoas Muscles / Q000294:innervation; D015203:Reproducibility of Results; D000077212:Ropivacaine; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000577:Amides; D000077212:Ropivacaine; D005041:Etidocaine