Quantitative measurement of blood remifentanil concentration: development of a new method and clinical application

Abstract

We have developed a new detection method of blood remifentanil concentration using a gas chromatography-mass spectrometry(GC-MS) with fentanyl as the internal standard(IS). The detection was performed at m/z 168 and 245 for remifentanil and fentanyl, respectively. In addition, the retention times of remifentanil and fentanyl were 5 min 45 s and 6 min 51 s, respectively. The standard curve of relationship between remifentanil concentration and the ratio of the peak area of remifentanil to fentanyl was satisfactorily fitted as linear regression (R(2) = 0.998, p < 0.01). Intra- and inter-assay CV was 10.5 and 11.5 %, respectively. In the clinical setting, 21 adult patients undergoing elective surgery under propofol-remifentanil TIVA were enrolled. To determine blood remifentanil concentrations, arterial blood was obtained at 0-30 min after cessation of remifentanil infusion at 0.2 μg/kg/min. Blood samples were given into sample tubes(chilled on ice) containing citric acid 50 % 60 μl which inactivates all esterase, and then stored at -20 °C until assay. Measured blood remifentanil concentration was 3.59 ± 0.74 ng/ml at the end of remifentanil infusion, and the ime for a decrease in blood remifentanil concentration by half was ~2 min. Remifentanil concentration was below the detection limit 30 min after the cessation. Thus, we have confirmed that this new method is clinically applicable.