Development of an ionic‐liquid‐based dispersive liquid–liquid microextraction method for the determination of antichagasic drugs in human breast milk: Optimization by central composite design

Abstract

Chagas disease constitutes a major public health problem in Latin America. Human breast milk is a biological sample of great importance for the analysis of therapeutic drugs, as unwanted exposure through breast milk could result in pharmacological effects in the nursing infant. Thus, the goal of breast milk drug analysis is to inquire to which extent a neonate may be exposed to a drug during lactation. In this work, we developed an analytical technique to quantify benznidazole and nifurtimox (the two antichagasic drugs currently available for medical treatment) in human breast milk, with a simple sample pretreatment followed by an ionic‐liquid‐based dispersive liquid–liquid microextraction combined with high‐performance liquid chromatography and UV detection. For this technique, the ionic liquid 1‐octyl‐3‐methylimidazolium hexafluorophosphate has been used as the “extraction solvent.” A central composite design was used to find the optimum values for the significant variables affecting the extraction process: volume of ionic liquid, volume of dispersant solvent, ionic strength, and pH. At the optimum working conditions, the average recoveries were 77.5 and 89.7%, the limits of detection were 0.06 and 0.09 μg/mL and the interday reproducibilities were 6.25 and 5.77% for benznidazole and nifurtimox, respectively. The proposed methodology can be considered sensitive, simple, robust, accurate, and green.

Modeling drug passage into human milk

“…67 The model has not been completely validated clinically, but a few breastmilk samples containing nifurtimox have been reported and appear to indicate that it may have an M/P ratio greater than 1. 68 Experience with nifurtimox indicates that simulations of new drugs should probably be based on reliable estimates of the M/P ratio, although a sensitivity analysis approach as used here can also be useful.…”

Dispersive Liquid-Liquid Microextraction in the Analysis of Milk and Dairy Products: A Review

“…Room temperature ionic liquids are another alternative green extraction solvent. Recently, in 2015, an IL-DLLME procedure was developed for the determination of nifurtimox (NFX) and benznidazole (BNZ) in breast milk coupled to HPLC-UV [37]. Proteins and lipids were removed by the addition of a precipitation mixture (HClO 4 , H 3 PO 4 , and methanol) followed by incubation at 80 ∘ C for 60 minutes.…”

Development of a dispersive liquid-liquid microextraction technique for the analysis of aryloxyphenoxy-propionate herbicides in soy-based foods

“…The advantages of IL-DLLME are the use of a small volume of ionic liquid, ease of operation, rapidity, low cost, high recovery for several compounds, high enrichment factors and environmentally friendly nature [22,23]. The extraction by IL-DLLME is based on a ternary solvent system: the aqueous sample, the dispersive solvent and the extraction solvent.…”