Worldwide Solutions - February 2008 - (Page 4) GERSTEL Solutions Worldwide Application Determining Organic Volatile Impurities (OVIs) in pharmaceutical products Organic Volatile Impurities – 4 minute cycle time! The production of pharmaceuticals is tightly regulated. US and European Pharmacopeia lay down the law: Pharmaceutical products must be analyzed for Organic Volatile Impurities (OVIs), the technique mainly used is Headspace GC. he conventional GC method used for the determination of solvent residues or Organic Volatile Impurities (OVIs) according to the European pharmacopeia typically requires a 35 minute GC run. When the Pfizer R&D Dept. in Sandwich, U.K. started looking into whether the analysis could be accelerated, they turned to the Research Institute for Chromatography (RIC) of Professor Pat Sandra. The result of the cooperation has now been published (J. Sep. Sci. 2006, 29, 695 – 698) and it shows that the method can be accelerated significantly. For the OVI determination, Pfizer was using a 6890 GC from Agilent Technologies equipped with a split/splitless inlet and a flame ionization detector (FID). The column used was a DB 624 type phase, 30 meters long, 320 µm i.d. with 1 µm film thickness. This column meets the requirements of the EU and US Pharmacopeia, enabling good separation of all listed polar and nonpolar solvents. The separation takes around 35 minutes, not counting the cool down time which in turn adds between 5 and 10 minutes depending on the ambient temperature in the laboratory. The aim was to shorten the GC cycle time, improving throughput and productivity, without changing the basic method. The RIC added a Modular Accelerated Column Heater (MACH) from GERSTEL to the 6890 GC. MACH enables mounting of up to 4 column modules with standard capillaries on the GC. MACH can be programmed to heat the column at rates of up to 1800 °C/min. Cool-down of the column from 240 to 40 °C is achieved in 30 to 60 seconds depending on the column length. T MACH is based on Low Thermal Mass (LTM) technology that only heats the GC column. Unlike standard GC ovens, MACH column modules do not use large amounts of insulation, metal chambers, and large volumes of air, all of which need to be heated and cooled over the course of a temperature programmed analysis cycle. Because MACH technology does not require the heating and cooling of these ancillary components, significantly shorter GC cycle times and higher sample throughput can be achieved. MACH is controlled from Agilent Technologies’ ChemStation software or directly through the MAESTRO software. Upgrade your GC in less than 30 minutes The 6890 GC was upgraded by replacing the standard oven door with a MACH system that can hold up to four modules. After about 30 minutes, MACH had been installed and the GC reconfigured and ready to run. Column modules were mounted on the outside of the GC using an opening in the MACH GC oven door. During the run, the GC oven is kept isothermal at high temperature. This means that no special accessories or connectors are required to keep the column ends and connectors heated, minimizing system complexity. Not having to cycle the GC oven temperature provides energy savings. No heating energy is expended to repeatedly heat the oven to high temperatures. This in turn means that less heat is released to the lab environment and subsequently that less energy is required for air conditioning in the summer. For the task at hand, the RIC chose a MACH module with a column that was shorter and with smaller internal diameter than the one originally used by Pfizer: DB 624 stationary phase, 25 meters long, 180 µm I.D. and 1 µm film thickness. This column provides more efficiency per unit length of column as well as enhanced speed of separation. The improvement was significant: Separation of a 20 solvent mixture was achieved in approximately 2.7 minutes – with good sensitivity, reproducibility, and linearity over a wide concentration range. Thanks to ultra-efficient cooling, the cycle time was reduced to a total of only 4 minutes. GC/MS-System from Agilent Technologies with the GERSTEL MultiPurpose Sampler (MPS XL) and GERSTEL Modular Accelerated Column Heater (MACH). GERSTEL Solutions Worldwide – February 2008 4
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