title: Assessment of tandem mass spectrometry and high-resolution mass spectrometry for the analysis of bupivacaine in plasma.
abstract: Triple quadrupole mass spectrometers coupled with high performance liquid chromatography are workhorses in quantitative bioanalyses. They provide substantial benefits including reproducibility, sensitivity and selectivity for trace analysis. Selected reaction monitoring allows targeted assay development but datasets generated contain very limited information. Data mining and analysis of nontargeted high-resolution mass spectrometry profiles of biological samples offer the opportunity to perform more exhaustive assessments, including quantitative and qualitative analysis. The objectives of this study were to test method precision and accuracy, to statistically compare bupivacaine drug concentration in real study samples and to verify if high-resolution and accurate mass data collected in scan mode can actually permit retrospective data analysis, more specifically, extract metabolite related information. The precision and accuracy data presented using both instruments provided equivalent results. Overall, the accuracy ranged from 106.2 to 113.2% and the precision observed was from 1.0 to 3.7%. Statistical comparisons using a linear regression between both methods revealed a coefficient of determination (R(2)) of 0.9996 and a slope of 1.02, demonstrating a very strong correlation between the two methods. Individual sample comparison showed differences from -4.5 to 1.6%, well within the accepted analytical error. Moreover, post-acquisition extracted ion chromatograms at m/z 233.1648 ± 5 ppm (M - 56) and m/z 305.2224 ± 5 ppm (M + 16) revealed the presence of desbutyl-bupivacaine and three distinct hydroxylated bupivacaine metabolites. Post-acquisition analysis allowed us to produce semi-quantitative evaluations of the concentration-time profiles for bupicavaine metabolites.
authors.affiliation: Centre de Recherche du Centre Hospitalier Universitaire de l'Université de Montréal, Montréal, Québec, Canada (CRCHUM).
authors.forename: Fleur
authors.initials: F
authors.lastname: Gaudette
authors.affiliation: Département de Sciences Cliniques, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, Québec, Canada.
authors.forename: Javier
authors.initials: J
authors.lastname: Benito
authors.affiliation: Groupe de Recherche en Pharmacologie Animal du Québec, Département de Biomédecine Vétérinaire, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, Québec, Canada.
authors.forename: Paulo
authors.initials: P
authors.lastname: Steagall
authors.affiliation: Centre de Recherche du Centre Hospitalier Universitaire de l'Université de Montréal, Montréal, Québec, Canada (CRCHUM).|Groupe de Recherche en Pharmacologie Animal du Québec, Département de Biomédecine Vétérinaire, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, Québec, Canada.
authors.forename: Francis
authors.initials: F
authors.lastname: Beaudry
mesh_terms: D000779:Anesthetics, Local / Q000097:blood*; D000818:Animals; D002045:Bupivacaine / Q000097:blood*; D002138:Calibration; D002415:Cats; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D057230:Limit of Detection; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000779:Anesthetics, Local; D002045:Bupivacaine
keywords: bioanalysis; bupivacaine; drug metabolism and pharmacokinetics; high resolution; liquid chromatography tandem mass spectrometry; orbitrap mass spectrometer; triple quadrupole mass spectrometer