Electromembrane extraction of substances with weakly basic properties: a fundamental study with benzodiazepines.

AIM: Electromembrane extraction (EME) of weakly basic benzodiazepines was investigated (-1.47 < pKa < 5.01).

MATERIALS & METHODS: 96-well EME was performed with strongly acidic conditions in the acceptor solution using 250-mM trifluoroacetic acid to maximize ionization.

RESULTS & CONCLUSION: Recoveries more than 80% were obtained for analytes with pKa > 2, whereas EME was less efficient for substances with pKa < 2. The latter was trapped in the supported liquid membrane due to less acidic pH conditions in the acceptor solution close to the supported liquid membrane. EME followed by UHPLC-MS/MS analysis was evaluated from human plasma, and the results were in compliance with EMA guidelines. Both electrokinetic migration and passive diffusion contributed to mass transfer when performing EME of weakly basic analytes.