title: Chromatographic determination of free lidocaine and its active metabolites in plasma from patients under epidural anesthesia.
abstract: OBJECTIVE
  We developed a simple and selective assay method for simultaneous determination of free lidocaine (LDC) and its active metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX) in plasma, by using high-performance liquid chromatography (HPLC). The method was applied to the plasma concentration monitoring in continuous epidural anesthesia with LDC.
  
  
  METHODS
  Free fraction was separated from plasma by using an ultrafiltration technique. Free and total LDC, MEGX and GX in plasma were analyzed by HPLC equipped with ordinary octadecylsilyl silica (ODS) column and ultraviolet (UV) detector.
  
  
  METHODS
  Five male patients with cancer who received epidural injection of 1.5% LDC for 5 hours in elective thoracic surgery, were enrolled to determine the plasma levels of total and free LDC, MEGX and GX.
  
  
  CONCLUSIONS
  The calibration curve for free LDC, MEGX and GX were linear at the concentration of 25 to 1,000 ng ml(-1) (r = 0.9998 - 0.9999). The recoveries for LDC, MEGX and GX from plasma water were ranged 73.2-89.1%. The coefficient variations for intra- and inter-day assay for LDC, MEGX and GX were less than 4.1%. The detection limit ofeach drug was 20 ng ml(-1). Plasma-free MEGX after 180 min epidural injection was higher than free LDC, even though the total concentration of MEGX was 4 times lower than that of LDC. The percentages of free fraction for LDC, MEGX and GX were 11.7, 48.5 and 78.3% after 5-hour epidural administration of LDC. Since the free fraction of MEGX and GX increases and exceeds the concentration of free LDC during continuous epidural anesthesia, accumulation of these toxic metabolites should be carefully monitored as well as LDC.
  
  
  CONCLUSIONS
  The present method is a reliable technique and can be applied to monitoring free LDC, MEGX and GX, which provide us beneficial information as to the LDC metabolism and toxicity.
authors.affiliation: Department of Pharmacy, Tsukuba University Hospital, Tsukuba, Ibaraki, Japan. ykaki@mail.hosp.tsukuba.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Kakiuchi
authors.forename: T
authors.initials: T
authors.lastname: Fukuda
authors.forename: M
authors.initials: M
authors.lastname: Miyabe
authors.forename: M
authors.initials: M
authors.lastname: Homma
authors.forename: H
authors.initials: H
authors.lastname: Toyooka
authors.forename: Y
authors.initials: Y
authors.lastname: Kohda
mesh_terms: D000328:Adult; D000767:Anesthesia, Epidural; D000779:Anesthetics, Local / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000097:blood* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D001798:Blood Proteins; D008012:Lidocaine; C001306:glycinexylidide; C001173:monoethylglycinexylidide