In my last blog post, “Challenging pharmaceutical impurity analyses Part 1 – Derivatization – first choice or last resort?” I looked into some of the issues that could occur when using derivatization. Life in the lab is challenging enough without adding additional preparation to samples.
Now, there is the other question of how to address the analysis of polar and ionic compounds. HPLC and GC can’t always offer the right chromatographic solutions for such analytes, even with a mass spectrometer attached.
There is a third, often underestimated, chromatographic technique, ion chromatography (IC), and guess what? You can hyphenate IC with a mass spectrometer, too!
IC in the Pharma Lab
You may already be familiar with IC for counter ion analysis or the USP assays for citrate, phosphate, and oxalate amongst others? And you know that new IC-based assays are incorporated into the USP modernization scheme.
Assays generally aren’t an issue; it is trace level impurities that offer the challenges, especially in complex matrices such as formulations.
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We previously mentioned the example of organic acids. These short-chained aliphatic compounds are often used as, or found in, starting materials, during the cleaning of production lines, or observed as byproducts. Therefore they need to be tracked through the development and production process.
- HPLC with weak anion exchangers and UV detection and ion-pairing chromatography will not give the desired sensitivity, especially in complex matrices.
- GC requires lengthy sample preparation of solid or liquid phase extractions or derivatization.
- Capillary electrophoresis can work, but often the desired sensitivity is not achieved. The capillary can be easily overloaded, and migration times can vary significantly. In short, this method isn’t really viable.
This is where ion chromatography helps: Anion exchange chromatography with a continuously regenerated membrane suppressor to desalt the mobile phase (eluent) yields low backgrounds, and high sensitivity and selectivity. Also, gradient elution can be applied to further improve separations through increased peak capacity. The permanent neutralization of high pH eluents allows the hyphenation to MS, boosting selectivity and sensitivity. Ion exchange is based on the elution by size, charge, and polarizability, and the stationary phases can be optimized to the chromatographic selectivity.
Also, did you know you can use IC and IC-MS for pharma and biopharma challenges such as glycans, amino acids, amines, aminoglycosides, carbohydrates, and sialic acids? This brochure contains more details.
Look out for part 3 where we will discuss what solutions make IC and IC-MS a perfect fit for pharma.
As always, you can speak to an expert if you want to discuss your challenges further.