Construction and clinical application of An analytical method for rapidly detecting sulfamethoxazole plasma concentration in heart transplant patients

OBJECTIVE To explore and establish an analysis method for sulfamethoxazole blood concentration in patients with heart transplantation to guide clinical rational drug use. METHODS A new two-dimensional liquid chromatograph (2D-LC-UV) based on column switching technology was used. The on-line solid-phase extraction of sulfamethoxazole in serum was performed using a one-dimensional column Aston SC2(3.5 mm×25 mm, 5 μm), then it was intercepted and retained through the middle column Aston SBR(3.5 mm×10 mm, 5 μm), and the target analytes were completely separated and detected by transfer to the second-dimension column Aston SNX4(4.6 mm×130 mm, 5 μm). The chromatographic conditions were obtained by optimization. The one-dimensional mobile phase was acetonitrile-methanol-H₂O(10:10:70), the flow rate was 0.8 mL·min^-1; the two-dimensional mobile phase ratio was BPI-1 basic mobile phase-API-3 acidic mobile phase-methanol(20:40:40) the flow rate was 1.2 mL·min^-1. The UV detection wavelength was 240 nm. RESULTS The correlation coefficient between the concentration of sulfamethoxazole and peak area was in the range of 9.96‒200.04 μg·mL^-1 with R²=0.999 6, it showed a good linear relationship. The intra-day and inter-day precisions(RSD) at low, medium and high concentrations were <15%, and the relative recoveries were between 85%‒115%. The blood concentration of 56 patients in the hospital was measured, and only 30 patients(53.57%) had the blood sample sulfamethoxazole concentration of 100‒150 μg·mL^-1, and the rest were not comfortable about the concentration treatment window; there were 0 cases of grade III-IV adverse reactions in the urinary system/blood system/liver, etc. CONCLUSION This method has a simple pre-treatment, high automation, can be sampled in large volumes, and has high accuracy and sensitivity. It can meet the requirements of clinical applications. The research results can provide a methodological reference for clinical therapeutic drug monitoring..