Solvent drying is a critical stage in many laboratory applications and light industrial processes, enabling the precise determination of a substance’s moisture content to ensure intermediates and finished goods meet standard specifications. Various methods of solvent extraction are available depending on the individual use case (molecular sieving, liquid-liquid extraction, etc.), and these drying processes require different infrastructures.
As solvent extraction is central to product quality, it is vital to ensure that these systems are operating successfully—and the cost of getting it wrong can be high. In pharmaceutical manufacturing, solvents typically account for up to 90% of mass utilization and are core contributors to the toxicity profiles of batch chemical operations.
So, how do you measure the success of your solvent drying process as part of a QA/QC workflow in pharmaceutical processing?
An Introduction to Loss-on-Drying
Assessing the success of solvent drying is often carried out by lab analysis, typically using the loss-on-drying (LOD) method. This thermogravimetric technique measures the weight change over time as a sample is heated, the central principle being that weight loss ceases once the substance has completely dried. A final measurement is compared to the initial sample weight and the difference indicates the total moisture content.
In the context of solvent drying quality assurance, the LOD method is used to define the amount of residual solvent in active pharmaceutical ingredients (APIs) and intermediates against a standard. Failure to meet that standard means the solvent drying process must be restarted, which poses operational challenges and leads to additional costs.
What is On-Line Gas Analysis?
On-line gas analysis is an advantageous alternative to the time-consuming LOD method. Typically comprising a process gas analyzer that samples from the dryer headspace, outlet, or vacuum chamber directly, this technique is faster and simpler than conventional solvent drying analysis techniques.
Among the best process gas analyzers for pharmaceutical solvent drying QA is the magnetic sector mass spectrometer (MS). This continuous mass spectrometer uses a magnetic field to separate ions by their mass-to-charge ratios, deflecting them to a detector as the magnetic flux density is scanned. As the acceleration voltage is kept constant, and the ions travel along the same curve path radius, the spectrometer can reliably detect ions of any mass at high resolution and across a high dynamic range. In practice, this means the analyzer can be used to continuously monitor the ion currents for principal solvents of interest with minimal spectral overlap between solvent fingerprints.
The magnetic sector mass spectrometer can exceed the performance capabilities of traditional quadrupole systems by a factor of up to ten times, and it can offer unparalleled precision, accuracy, and resistance to contamination—which is an issue with conventional mass spectrometry-based on-line process gas analyzers.
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