Introduction to Pharmaceutical Analysis: Extraction Techniques

This set of flashcards covers extraction techniques in pharmaceutical analysis, including solid-liquid and liquid-liquid extraction, supercritical fluid extraction, and the principles and materials used in solid phase extraction (SPE).

Extraction Techniques

Methods used to separate analytes from materials in a formulation matrix, often using a solvent in which the analyte is highly soluble but matrix components have limited solubility.

Saxis alba L. (White willow)

A natural source used for the solid-liquid extraction of Salicillin, which is associated with Aspirin.

Papaver somniferum L. (Opium poppy)

A natural source from which Morphine is extracted through solid-liquid extraction.

Soxhlet extractor

An apparatus used for the continuous solid-liquid extraction of compounds.

Partition coefficient ($P$)

A measure of extraction efficiency

liquid-liquid extraction

• place analyte solution solution (S1)

• add S2, stopper the funnel, shake the phases and allow to settle

• drain the lower layer into a beaker stopcock

• remove the upper layer by pouring out of the top of the funnel

• evaporate the solvent using vacuum and/or heat, or gas flow

Organic Acids and Bases Solubility

Free unionised acids and bases are generally soluble in organic solvents, whereas their salt forms are highly water soluble. Approximately $20\%$ of drugs are weak organic acids and $75\%$ are weak organic bases.

Liquid-liquid extraction for an organic base

1. direct removal of neutral and acidic excipients

2. acidic excipients left behind in aqueous layer

3. neutral excipients left behind in organic layer

Supercritical Fluid ($SCF$)

A substance above its critical temperature and pressure that exhibits gas-like viscosity and liquid-like density.

Carbon dioxide ($CO_2$) in SFE

The most frequently used supercritical fluid because it is non-toxic and non-flammable, with a critical temperature of $31.1\,^{\circ}C$ and a critical pressure of $73.8\,bar$.

Conditioning

The first step in Solid Phase Extraction ($SPE$) where the adsorbent is prepared.

Sample Addition

The second step in $SPE$ where the analyte is "dead-stopped" on the medium using a solvent of low eluting power.

Washing

The third step in $SPE$ where the medium is washed with solvents of low eluting power to remove contaminants/interferents.

Elution

The final step in $SPE$ where the analyte is removed using a small volume of solvent with high eluting power.

SPE Cartridge Adsorbant

The material inside an $SPE$ cartridge, typically consisting of $40\text{-}50\,\mu m$ particles and weighing between $50\text{-}500\,mg$.

Styrene-divinylbenzene polymer gels

SPE adsorbents that are more lipophilic and have a higher loading capacity than coated silica gels.

Borate gels

Selective $SPE$ adsorbents used for $1,2\text{-}$ and $1,3\text{-diols}$, such as catechols and glycosides.

Immunoaffinity gels

SPE adsorbents where a ligand with high affinity for a target analyte, such as an antibody, is attached to the surface.

Molecularly Imprinted Polymers ($MIPs$)

Organic polymers designed with pre-determined selectivity for specific analytes, often referred to as "plastic antibodies."