Polymer inclusion membrane sampling probe for electric field driven extraction of doxorubicin

Abstract

Sample preparation for the analysis of biological fluid samples posed significant challenges to the clinical laboratory. The current sample preparation practice involves multi-steps procedure that are time consuming and may lead to analytes lost. In this study, a low-cost, single-use sampling probe was introduced for electric field driven extraction. The sampling probe consists of a non-conductive glass capillary substrate, and a polymer inclusion membrane (PIM) dip-coated on the glass capillary substrate. The probe features a user-friendly design that can electrically extract targeted analytes from biological fluid sample. The glass capillary, closed at one end, was dipped in a homogeneous membrane solution that consists of an optimum composition of cellulose triacetate (CTA), 2-nitrophenyl octyl ether (2-NPOE) and 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMIM][NTf2]), yielded a PIM with thickness of 30 μm on the sampling probe. The effects of dipping cycles (thickness), voltage applied, and sample pH on the extraction efficiency of the sampling probe were thoroughly investigated. The concept of electrokinetic extraction using the PIM sampling probe was first demonstrated on the cationic model analyte, Rhodamine 6G at 500 V for 60 mins. The proven concept was then successfully applied to the extraction of the anticancer drug doxorubicin from samples in liquid or dried form, including dried blood spot (DBS), human plasma and human serum samples. The practicability and reliability of the electrokinetic extraction process were evaluated using liquid chromatography with tandem mass spectrometry (LC-MS/MS) to quantify the desorption of extracted doxorubicin from the PIM sampling probe. Under optimised conditions, the new method provided good linearity over a concentration range of 0.2 to 20 ng/mL; additionally, quantification limits of 0.2 to 2 ng/mL were achieved for the three biological samples and the relative recoveries ranged from 82.7 to 113.8% for DBS, human plasma and human serum samples; good method reproducibility was also achieved, with relative standard deviations (RSDs) ranging from 0.9 and 4.6%. The PIM sampling probe was further integrated into a portable battery-device for safe, lower-voltage (36 V) electrokinetic extraction. The correlation coefficients, r, for the two pairs of data were determined using the laboratory setup and the battery-powered device; values in the range of 0.9926 to 0.9996 were found, indicating an acceptable agreement. This new electrokinetic extraction approach represents a new opportunity for processing samples during sampling and transportation, saving time and reducing manual handling to produce more reliable test results efficiently.