TY - JOUR

T1 - Electromembrane extraction of peptides based on hydrogen bond interactions

AU - Dowlatshah, Samira

AU - Hansen, Frederik André

AU - Zhou, Chen

AU - Ramos-Payán, María

AU - Halvorsen, Trine Grønhaug

AU - Pedersen-Bjergaard, Stig

N1 - Funding Information: This work was funded by the Research Council of Norway (Grant 286555 ).

PY - 2023

Y1 - 2023

N2 - Background: Electromembrane extraction (EME) of peptides reported in the scientific literature involve transfer of net positively charged peptides from an aqueous sample, through a liquid membrane, and into an aqueous acceptor solution, under the influence of an electrical field. The liquid membrane comprises an organic solvent, containing an ionic carrier. The purpose of the ionic carrier is to facilitate peptide solvation in the organic solvent based on ionic interactions. Unfortunately, ionic carriers increase the conductivity of the liquid membrane; the current in the system increases, the electrolysis in sample and acceptor is accelerated, and the extraction system tend to be unstable and suffers from drifting pH. Results: In the present work, a broad selection of organic solvents were tested as pure liquid membrane for EME of peptides, without ionic carrier. Several phosphates provided high mass transfer, and tri(pentyl) phosphate was selected since this solvent also provided high operational stability. Among 16 different peptides used as model analytes, tri(pentyl) phosphate extracted those with net charge +1 and with no more than two polar side chains. Tri(pentyl) phosphate served as a very strong hydrogen bond acceptor, while the protonated peptides were hydrogen bond donors. By such, hydrogen bonding served as the primary interactions responsible for mass transfer. Tri(pentyl) phosphate as liquid membrane, could exhaustively extract leu-enkephalin, met-enkephalin, and endomorphin from human blood plasma and detected by LC-MS/MS. Calibration curves were linear (r2 > 0.99) within a concentration range from 1 to 500 ng/mL, and a relative standard deviation within 12% was observed for precision studies. Significance: The current experiments are important because they indicate that small peptides of low polarity may be extracted selectively in EME based on hydrogen bond interactions, in systems not suffering from electrolysis.

AB - Background: Electromembrane extraction (EME) of peptides reported in the scientific literature involve transfer of net positively charged peptides from an aqueous sample, through a liquid membrane, and into an aqueous acceptor solution, under the influence of an electrical field. The liquid membrane comprises an organic solvent, containing an ionic carrier. The purpose of the ionic carrier is to facilitate peptide solvation in the organic solvent based on ionic interactions. Unfortunately, ionic carriers increase the conductivity of the liquid membrane; the current in the system increases, the electrolysis in sample and acceptor is accelerated, and the extraction system tend to be unstable and suffers from drifting pH. Results: In the present work, a broad selection of organic solvents were tested as pure liquid membrane for EME of peptides, without ionic carrier. Several phosphates provided high mass transfer, and tri(pentyl) phosphate was selected since this solvent also provided high operational stability. Among 16 different peptides used as model analytes, tri(pentyl) phosphate extracted those with net charge +1 and with no more than two polar side chains. Tri(pentyl) phosphate served as a very strong hydrogen bond acceptor, while the protonated peptides were hydrogen bond donors. By such, hydrogen bonding served as the primary interactions responsible for mass transfer. Tri(pentyl) phosphate as liquid membrane, could exhaustively extract leu-enkephalin, met-enkephalin, and endomorphin from human blood plasma and detected by LC-MS/MS. Calibration curves were linear (r2 > 0.99) within a concentration range from 1 to 500 ng/mL, and a relative standard deviation within 12% was observed for precision studies. Significance: The current experiments are important because they indicate that small peptides of low polarity may be extracted selectively in EME based on hydrogen bond interactions, in systems not suffering from electrolysis.

KW - Electromembrane extraction

KW - Extraction

KW - Peptides

KW - Sample preparation

U2 - 10.1016/j.aca.2023.341610

DO - 10.1016/j.aca.2023.341610

M3 - Journal article

C2 - 37524472

AN - SCOPUS:85164712157

VL - 1275

JO - Analytica Chimica Acta

JF - Analytica Chimica Acta

SN - 0003-2670

M1 - 341610

ER -