Microfluidic chip capillary electrophoresis coupled with electrochemiluminescence for enantioseparation of racemic drugs using central composite design optimization

Optimization based on central composite design ( CCD ) for enantioseparation of anisodamine ( AN ), atenolol ( AT ), and metoprolol ( ME ) in human urine was developed using a microfluidic chip‐ CE device. Coupling the flexible and wide working range of microfluidic chip‐ CE device to CCD for chiral separation of AN , AT , and ME in human urine, a total of 15 experiments is needed for the optimization procedure as compared to 75 experiments using the normal one variable at a time optimization. The optimum conditions obtained are found to be more robust as shown by the curvature effects of the interaction factors. The developed microfluidic chip‐ CE ‐ ECL system with adjustable dilution ratios has been validated by satisfactory recoveries (89.5–99% for six enanotiomers) in urine sample analysis. The working range (0.3–600 μM), repeatability (3.1–4.9% RSD for peak height and 4.0–5.2% RSD for peak area), and detection limit (0.3–0.6 μM) of the method developed are found to meet the requirements for bedside monitoring of AN , AT , and ME in patients under critical conditions. In summary, the hyphenation of CCD with the microfluidic chip‐ CE device is shown to offer a rapid means for optimizing the working conditions on simultaneous separation of three racemic drugs using the microfluidic chip‐ CE device developed.