Stereoselective high-performance liquid chromatographic assay with fluorometric detection of the three isomers of mivacurium and their cis- and trans-alcohol and ester metabolites in human plasma.
An improved high-performance liquid chromatography assay for the three stereoisomers of the muscle relaxant mivacurium and its metabolites in plasma is presented. The principal steps in the assay are precipitation of plasma proteins by acetonitrile, lyophilization of the supernatant and ion-exchange chromatography on Spherisorb 5-SCX column, with gradient elution (acetonitrile from 32 to 68% v/v and ionic gradient from 7 to 56 nmol l-1 Na2SO4), a flow-rate of 2.0 ml min-1, D-tubocurarine as internal standard and fluorometric detection (excitation wavelength = 280 nm, emission wavelength = 320 nm). Quantitation limit of cis-cis, cis-trans, trans-trans isomers were 0.003, 0.002 and 0.005 mumol l-1, respectively. Quantitation limits for the monoestercis metabolite were 0.011 mumol l-1, for the monoestertrans metabolite 0.017 mumol l-1, for the amino-alcoholtrans 0.020 mumol l-1 and for the amino-alcoholcis 0.021 mumol l-1. None of eight drugs used during anaesthesia interfered with the assay in vitro. Satisfactory performance was demonstrated by the measurement of the isomers and their metabolites in plasma of two patients over a 6-h period after repeated injections of mivacurium.
Biederbick
W
W
University of Cologne, Department of Pharmacology, Germany.
Aydinciouglou
G
G
Diefenbach
C
C
Theisohn
M
M
D000438:Alcohols / Q000737:chemistry; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004952:Esters / Q000737:chemistry; D005470:Fluorometry; D006801:Humans; D007275:Injections, Intravenous; D007546:Isoquinolines / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D016014:Linear Models; D000077590:Mivacurium; D003473:Neuromuscular Nondepolarizing Agents / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D015203:Reproducibility of Results; D013237:Stereoisomerism; D013997:Time Factors
D000438:Alcohols; D004952:Esters; D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D000077590:Mivacurium