---
title: Sample preparation by mixed-mode SPE using ISOLUTE® HCX
description: This technical note describes the extraction of basic drugs from biological fluids using ISOLUTE® HCX mixed-mode SPE products.
---

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# [Sample preparation by mixed-mode SPE using ISOLUTE® HCX](https://www.biotage.com/literature/technical-note/sample-preparation-mixed-mode-spe-isolute-hcx)

 Written by [Biotage](https://www.biotage.com/literature/author/biotage) | Dec 10, 2025 1:14:33 PM

This technical note describes the extraction of basic drugs from biological fluids using ISOLUTE® HCX mixed-mode SPE products.

Sample preparation techniques such as protein precipitation, supported liquid extraction or non-polar SPE may not be selective enough to give extracts of sufficient purity for low level analysis. In these cases, the selective mixed-mode approach to the extraction of basic drugs is a suitable alternative, giving very high purity extracts with minimal levels of co-extracted material.

The ISOLUTE® HCX series of mixed-mode SPE sorbents (ISOLUTE HCX, HCX-3 and HCX-5) are based on a combination of strong cation exchange and non-polar (C8, C18 and C4 respectively) chemistries. Basic drugs are retained by two primary retention mechanisms (see Figure 1). This allows a rigorous interference elution regime to be used to elute interferences retained by either non-polar or cation exchange interactions alone. Only analytes with both non-polar and basic characteristics are extracted using the ISOLUTE HCX series of sorbents, providing an extremely pure final extract.

Literature number: TN125.V.2

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