Uncovering Hidden Chemical Risks in Pharmaceutical Packaging and Medical Devices

Hyphenated chromatography-mass spectrometry techniques, where two or more analytical techniques are integrated into a single system, significantly enhance analytical performance by improving sensitivity, selectivity and data quality:

• A high sensitivity technique allows detection of target substances at ultra-low concentrations, making it indispensable for trace- and micro-level analysis
• A high selectivity technique enables efficient separation and confident identification of target analytes within complex matrices
• Data-rich outputs generate multidimensional datasets (e.g. accurate mass and retention time), streamlining complex data processing and enhancing result reliability

SGS solutions

We have established a robust analytical workflow backed by years of industry expertise, using the following key steps:

1. Spectral analysis: evaluating mass spectra to identify diagnostic fragments and determine accurate molecular weights
2. Formula prediction: derivation of elemental compositions and potential structural units using mass defects, isotopic abundance ratios and degrees of unsaturation
3. Material context: application of polymer chemistry knowledge, including synthesis monomers, polymerization pathways and common additives, to guide and validate structural assignments
4. Comprehensive verification: correlating all gathered data to assign fragments to confirm the proposed chemical structures

With this high-resolution and high-quality compositional dataset, a detailed breakdown of components is generated, allowing businesses to demonstrate reliable bioanalytical outcomes and accelerate clinical development timelines.

Our comprehensive expertise integrates advanced technologies, validated workflows and extensive regulatory knowledge to deliver high-sensitivity, reproducible characterization of complex chemical substances. Supported by a global network of accredited facilities, we enable the delivery of safe, high-quality and efficiently developed products.

Case study: identification of PES oligomers

Advanced mass spectrometry (MS) techniques play a critical role in extractables and leachables (E&L) analysis, enabling the identification of unknown compounds at trace levels in pharmaceutical packaging and medical devices.

Using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) in negative electrospray ionization (ESI$^-$) mode, three unknown compounds were detected in extracts obtained from a polyethersulfone (PES) medical device. Their mass spectra are shown in Figure 1.

1. MS spectrum analysis and molecular formula prediction

Accurate molecular weights were determined from high-resolution mass spectral data. By applying established principles such as mass defect analysis, isotopic distribution and rings-plus-double-bonds equivalents (RDBE) calculations, the elemental compositions were determined as:

C30H21O9ClS3, C42H29O12ClS4, C54H37O15ClS5

The systematic increase in molecular size and composition indicates a homologous series, a typical feature of polymer-related extractables.

2. Evaluation of polymer monomers and synthesis processes

Polyethersulfone (PES) is typically synthesized via the polycondensation of bisphenol S (BPS) and 4,4'-dichlorodiphenyl sulfone (DCDPS). BPS acts as a nucleophile that reacts with DCDPS. Specifically, the hydroxyl group 9(-OH) of BPS attacks the chlorine-bearing DCDPS, forming a new C-O ether bond while releasing a chloride ion. As the polymerization proceeds, the two hydroxyl groups of BPS react with the two chlorine atoms of DCDPS, building the repeating unit of the PES chain. The synthetic pathway is illustrated in Figure 2.

3. Structural elucidation via MS fragment patterns

The quasi-molecular ions of the three compounds shown in Figure 1 (m/z 655, 887 and 1119) exhibit a consistent mass difference of 232 Da. This neutral loss corresponds to a C12H8O3S unit, which can be assigned to a 4-(phenylsulfonyl)phenol-related moiety. This pattern strongly indicates that the compounds are PES oligomers.

4. Consolidated result verification

By integrating the mass spectral data with material-specific chemical knowledge, the unknown compounds were successfully identified as linear PES oligomers. Their chemical structures and IUPAC names are shown in Figure 3.