When Chiral Separation Turns Tricky: The Story Behind CESI-MS in Forensic Chiral Analysis

Against a backdrop of rapid growth, chirality plays a major role in the synthesis of drugs in both pharmaceutical and illicit drug development. In fact, more than half of the drugs currently in use are chiral compounds, available as either racemates or pure enantiomers. With increasing substances of forensic interest falling within this category, chiral analysis is firmly under the forensic microscope.

As a forensic toxicologist, you could be using chiral analysis in biological samples to determine legal or illicit drug consumption. Or perhaps you are working with street samples to link a clandestine lab with their route to market or even environmental samples to identify illicit drug manufacturing locations. Whatever your field, chiral separation of drug enantiomers is essential in order to show that the active enantiomer is, in fact, present in your specimens.

So how do you do your chiral analysis right now and are you using the right technology?

In the past, chiral analysis has combined several processes. It would typically start with drug confirmation by a form of mass spectrometry (capillary electrophoresis CE-MS, gas chromatography GC-MS or liquid chromatography LC-MS) followed by separation of the enantiomers and impurities by a specific chiral separation technique, such as chiral capillary electrophoresis or chiral chromatography. It’s fair to say that this approach can be problematic, would you agree?

We’ve found that direct connection of chiral GC or LC columns with mass spectrometry provides, at best, marginal separation capability. But that’s not all. Neutral or highly sulfated cyclodextrin additives in chromatographic and electro-driven separation modes can cause contamination and ion suppression in the electrospray process. This is far from ideal!

So, you ask, where does CESI-MS come in?

Have you heard of low flow Capillary Electrophoresis Electrospray Interface for Mass Spectrometry (CESI-MS) using a Partial Filling Technique (PFT)? It’s proven to generate chiral separation and produce quantitative data at the sensitivity that forensic toxicologists require for even the most challenging casework.

We put the method to the test in the tech note Chiral Analysis of Methamphetamine and Its Metabolite, Amphetamine in Urine by CESI-MS. This new technique separated the enantiomers of methamphetamine and its metabolite, amphetamine, in a single run, with great sensitivity.

Use the form on the right to download the Forensics Compendium to see the complete method, along with recent advancements developed by the forensics team and how mass spec technology is defining forensics of the future.