title: Therapeutic monitoring of tranexamic acid concentration: high-throughput analysis with solid-phase microextraction.
abstract: BACKGROUND
  The controversy still surrounds the optimal dosing regimen of tranexamic acid (TA), primary antifibrinolytic agent used in high-risk surgeries. This study compares the pharmacokinetics profile obtained from the group of patients undergoing heart surgery with the use of cardiopulmonary bypass (CPB) with the theoretical model currently used as an established dosing regimen of TA in cardiac surgery.
  
  
  METHODS
  After induction of anesthesia, TA was administered intravenously as a bolus (30 mg/kg) infused over 15 minutes. Bolus was followed by an infusion of 16 mg·kg·h TA until the end of surgery (chest closure of the sternotomy wound). Before initiation of CPB, a bolus of 2 mg/kg was given to the pump prime. Blood samples were collected at baseline and at 30-minute time intervals during the surgery and after surgery. Automated solid-phase microextraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used for the determination of TA concentration. Blinded studies on monitoring of TA concentration were performed on 94 samples. Obtained results were compared with a previously described pharmacokinetic model of TA dosing.
  
  
  RESULTS
  The average concentration of TA during the use of CPB was 134 mcg/mL with the relative standard deviation 27%. The observed range of TA concentrations was 70-188 mcg/mL showing that individual patients can significantly exceed the recommended levels proposed by the theoretical model. lower limit of quantification of the proposed method was 1 mcg/mL. Intra- and interday accuracy was ±10% and precision was ≤12% at all concentration levels tested.
  
  
  CONCLUSIONS
  The suitability of automated solid-phase microextraction for high-throughput clinical analysis was established for the first time. The obtained pharmacokinetic profiles showed significant interpatient variation in the concentration of TA during heart surgery with the use of CPB, which confirms the need of the therapeutic monitoring of this antifibrinolytic agent.
authors.affiliation: Department of Chemistry, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bojko
authors.forename: Dajana
authors.initials: D
authors.lastname: Vuckovic
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Mirnaghi
authors.forename: Erasmus
authors.initials: E
authors.lastname: Cudjoe
authors.forename: Marcin
authors.initials: M
authors.lastname: Wasowicz
authors.forename: Angela
authors.initials: A
authors.lastname: Jerath
authors.forename: Janusz
authors.initials: J
authors.lastname: Pawliszyn
mesh_terms: D000933:Antifibrinolytic Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D015203:Reproducibility of Results; D052617:Solid Phase Microextraction / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods; D014148:Tranexamic Acid / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*
chemical_list: D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid