shutterstock_72309415When we are sick we rely heavily on chemistry to quickly restore our health and make us fully operational again. I’ve been experiencing this for a couple of weeks now, trying to eradicate resistant bacteria in my body … but is there only good chemistry in my tablets? Certainly there is good chemistry (active pharmaceutical ingredients) that helps us to recover from illness, but what’s not so apparent is the lengths that pharmaceutical companies go to to ensure that the medicines we are using are as pure as possible.

Pharmaceutical manufacturers put a high priority on controlling the quality and safety of their products.  A key part of this is rigorous chemical analysis, in both qualitative and quantitative terms, to monitor for potential impurities arising from possible variances in the manufacturing process — such as raw materials or from contact materials in packaging, for example.

Especially during the pharmaceutical development, impurity profiling and subsequent QA/QC is a critical aspect which aims to identify and quantify organic and inorganic impurities, as well as residual solvents in bulk drugs and pharmaceutical formulations.

Various regulatory authorities like ICH (International Conference on Harmonization), USFDA (United States Foods and Drugs Administration), UK-MHRA (UK Medicines and Healthcare Products), and Indian CDSCO (Central Drugs Standard Control Organization) are emphasizing their compliance requirements regarding the identification of impurities in Active Pharmaceutical Ingredients (APIs) and finished products [1].

Due to high levels of regulatory control, it is not surprising that the control of pharmaceutical impurities in a compliant manner is currently a critical and challenging issue to the pharmaceutical industry.

Several analytical methods are typically used for impurities identification and quantitation, but considering organic volatile impurities like residual solvents or volatile extractable and leachable organic compounds, gas chromatography is the technique of choice.

The Simplicity of the Headspace GC Sampling Technique

There is not a much easier method, in terms of sample preparation, than taking your solid sample, putting it into a sealed 10 mL or 20 mL vial with a few mL of water and dissolving it.

This is the benefit of the Headspace Sampling technique which relies on the equilibrium of volatile compound concentration established between the solid phase (sample) and the gas phase above it (headspace) into a sealed vial. After the equilibrium is established during a heated incubation period, which can span between 10 and 30 minutes, an aliquot of the headspace is injected into the GC or GC-MS system to get a comprehensive profiling of the volatile fraction [2].

The technique is so easy and fully automated that it is extensively used worldwide in routine testing laboratories involved in pharmaceuticals QA/QC assessment for residual solvent analysis according to USP chapter <467> methodology.

Resource: Routine-grade performance of a new static headspace autosampler for the analysis of residual solvents according to USP <467> method

Resource: Simplified, cost-effective headspace GC method for residual solvents analysis in pharmaceutical products

 When Innovation Drives Productivity

Pittsburgh Conference 2019 was another amazing event characterized by several product innovations aiming to increase the productivity and the efficiency of modern laboratories while raising the bar of the analytical performance standards.

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During the exhibition, we were very proud to present our new TriPlus 500 Headspace GC autosampler which offers a breakthrough for volatiles GC analysis thanks to its innovative and original design.

Technological advances like a direct column connection and a new proprietary pneumatic control were at the base of this product development to offer customers a robust and reliable workflow solution; easy to use and scalable in sample throughput capability; high analytical performance in terms of injection precision; and sample integrity during transfer and routine grade robustness assure extended unattended operations joint to high quality of the data, to be right the first time. Performance specifications are consistently met at the first trial allowing customers to streamline validation procedures.

Resource: Productivity from all angles – Thermo Scientific TriPlus 500 Gas Chromatography Headspace Autosampler

With this fresh approach, the TriPlus 500 HS is perfectly positioned to tackle the difficult challenges faced by routine laboratories for residual solvents analysis for QA/QC testing, and when connected to the powerful Thermo Scientific GC-MS portfolio, offers many options to accelerate progress in R&D and method development laboratories.

Recently, we had the opportunity to collaborate with a multinational contract testing organization, SGS, at their Fairfield (NJ) site in the area of extractables and leachables, as well as residual solvents analysis. During this collaboration, SGS had the opportunity to test the TriPlus 500 HS autosampler coupled with a Thermo Scientific Trace 1310 GC-FID, as well as a Thermo Scientific Orbitrap GC-MS system for unknown volatile impurities identification.  You can learn more about their experiences here.

Regulatory Compliance

During pharmaceutical analysis, compliance and adherence to data quality guidelines is a critical. Both procedural and technical controls must be in place to ensure data integrity is not compromised, while system qualification must provide evidence that the instrument performs suitably for its intended purposes, matching the User Requirement Specification (URS), in compliance with USP <1058> [3].

Thermo Scientific Chromeleon CDS software is the right answer for all those laboratories in pain with compliance duty, offering automated qualification tools, wizard driven workflow and security tools for data integrity.

Taking my medicine this morning I thought about all the effort going into ensuring a safe and high quality product … and I started feeling better!

References

[1]  A Chanda, N Ramalakshmi, CN Nalini, S Mahabubi, “Impurity profiling an emerging trend in Pharmaceuticals: A Review”, PharmaTutor, 2015; 3(11); 29-35

 [2] Bruno Kolb and Leslie S.Ettre, “Static Headspace-Gas Chromatography, Theory and Practice”, Wiley, (2006)

[3] https://hmc.usp.org/sites/default/files/documents/HMC/GCs-Pdfs/c1058.pdf