Purpose: Solid phase microextraction (SPME) is a technique widely used and accepted in the field of food technology and in environmental and biological analyses. Despite its numerous advantages over older analytical methods, it has not been studied extensively in the medical sciences. Tranexamic acid (TXA) is currently the sole antifibrinolytic agent used during cardiac surgery involving the use of cardiopulmonary bypass (CPB). The current standard method of measuring TXA in plasma is based on plasma protein precipitation (PPP), but this analytical approach is time-consuming and not practical for routine use. The aim of the current study was to compare plasma TXA levels measured with the PPP method vs those acquired with the novel, highly efficient SPME technique. We also investigated the use of automated SPME with the aim of improving the technique so it could be used efficiently for measuring plasma TXA levels.
Methods: With Research Ethics Board approval, we undertook a prospective, investigator-blinded study in ten patients undergoing cardiac surgery with CPB. An initial TXA bolus of 30 mg·kg(-1) was infused over 15 min followed by a 16 mg·kg(-1)·hr(-1) infusion until chest closure with a 2 mg·kg(-1) load in the pump prime. Each blood sample was divided into two portions and assigned a random number to blind the analyzing laboratory. The blood TXA concentration was measured using both PPP and SPME. Agreement between the two tests was analyzed using the Bland-Altman plot.
Results: Comparisons of plasma TXA concentrations measured with the two methods (PPP and SPME) showed good agreement. Absolute recovery of TXA for PPP was 64.9-78.2%; its precision, as a percentage of the relative standard deviation (RSD) was < 10% [with the exception of the lower limit of quantification (LLOQ), where the RSD was 18%]; and its accuracy, as the bias against the nominal concentration, was < 7% (for LLOQ it was 15%). Thus, extraction with SPME compared favourably with the PPP technique.
Conclusions: Solid phase microextraction is a relatively simple, rapid extraction technique that can facilitate future pharmacokinetic studies analyzing TXA drug concentrations and drug dosing in various clinical settings.