A simple and selective liquid chromatography- tandem mass spectrometry method for determination of ε-aminocaproic acid in human plasma

Intraoperative hemorrhage during pediatric craniofacial reconstruction and other surgical procedures can be significant and may exceed the circulating blood volume [1] mandating substantial perioperative transfusion. The intraoperative administration of antifibrinolytic agents is increasingly used to minimize blood loss and the need for transfusion [2]. Fibrin binding by tissue-type plasminogen activator and plasminogen is the key to the initiation of fibrinolysis. Plasmin is generated and cleaves fibrin, producing new C-terminal lysines, which serve to mediate positive feedback in the fibrinolytic cascade [3]. Downregulation of fibrinolysis in vivo occur through the action of carboxypeptidases, which remove C-terminal lysines [4]. The antifibrinolytic epsilon-aminocaproic acid (EACA) is a synthetic lysine analogue that blocks the lysine-binding sites on plasminogen, resulting in antifibrinolytic activity through inhibition of plasmin formation [5, 6] and ultimately clot stabiliziation. The objective of this investigation was to develop and validate a simple and selective liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the quantification of EACA in human plasma to support clinical pharmacokinetic studies of EACA in pediatric patients. There were several HPLC methods reported in the literature for analysis of EACA in biological samples. EACA was dansylated and measured by fluorescence detection [7] with an assay range of 50 to 1000 μg/mL in human serum. A similar HPLC-fluorimeter assay with a range of 62.5 to 1000 μg/mL was reported by Lacroix C et.al. [8]. An assay for EACA in plasJOURNAL OF APPLIED BIOANALYSIS, July 2015, p. 99-107. http://dx.doi.org/10.17145/jab.15.016 (ISSN 2405-710X) Vol. 1, No. 3