Synthesis of Isotopic Labelled Paracetamol Benzoate-d3 and Its Application in the Determination of Paracetamol

This study proposed a precise/accurate analytical method for the paracetamol (PCT) determination in human serum/urine matrices. PCT was simultaneously derivatized and preconcentrated by dispersive liquid-liquid microextraction (DLLME). Benzoyl chloride dissolved in dichloromethane was used as derivatization agent in the extraction solvent. Quadruple isotope dilution (QID) method with three calibration mixtures (A*B-x, x=1,2,3) and one sample mixture (AB) was performed to enhance the method accuracy and precision. In our research laboratory, paracetamol benzoate-d3 (PCT benzoate-d3) was synthesized and used as isotopically labelled substance (B) to conduct QID method. After the combination of QID and DLLME-GC-MS systems, percent recovery results for human serum/urine matrices were found to be 99.3-101.0 % and 98.8-99.9 %, respectively.

Automated summary

This study developed a precise method for determining paracetamol in human serum and urine using dispersive liquid-liquid microextraction. The method involved derivatization of paracetamol and preconcentration using benzoyl chloride dissolved in dichloromethane. Quadruple isotope dilution (QID) was employed to enhance the accuracy and precision of the method. The combination of QID and DLLME-GC-MS systems resulted in high percent recovery for both serum and urine matrices.