Blog Post 11 – Crystals in Bloom: Unraveling the Solubility Puzzle
2 min reading time
Followers of our blog series will notice that a routine ultraviolet (UV) liquid chromatography (LC) analysis is often the first step in detecting that something is wrong with a drug product. Unexpected impurities that breach the identification or qualification threshold require further investigation. What follows can be a range of strategies to identify the chemical component(s) responsible – and even more importantly, to determine the root cause of their presence in the production process.
However, as in the previous post, the human eye can also spot problems. In this case, a medical device exhibited “blooming” caused by tiny crystals. At first glance, blooming simply makes the device look unattractive. More importantly, though, is understanding the chemical nature of the phenomenon and whether it poses any toxicological risk.
The customer who contacted us suspected “a kind of lubricant” and agreed to a two-step approach to identify the molecule causing the blooming.
The first step involved scraping and dissolving some crystals in isopropanol (IPA), a strong solvent, followed by our routine LC–Mass Spectrometry (MS) screening. This method is designed to ionize and detect as many nonvolatile extractables and leachables as possible. Its strength lies in the extensive set of chemicals included in our Nelson Labs proprietary screener database.
As a second step – if the screening results were inconclusive – we proposed a dedicated analysis using high-end equipment and multiple ionization sources to fragment and piece together the structure.
Figure 1: From sampling, routine screening and identification to confirmation with an authentic standard.
The screening chromatogram revealed one dominant peak, readily identified via our screener database as Bisphenol A. Measuring a freshly prepared Bisphenol A standard solution in isopropanol confirmed the identification. The root cause of the Bisphenol A crystals was its addition to the device’s polymer beyond its solubility limit.
As with other blooming projects we’ve handled, the initial screening step was sufficient to resolve this insolubility issue reinforcing once more the advantages of our proprietary screener database of relevant mass spectra and stock of relevant extractables and leachables chemicals.
If you have additional questions about Impurities Identification test services or would like to consult with the experts at Nelson Labs, just send an e-mail to [email protected].
