Translating Monograph Chromatography Methods to Smaller Dimension Columns with Porous and Solid Core particles Using new Guidance from USP <621>

Compendial tests and other product specific tests are necessary to assure the safety and quality of human medicinal products manufactured around the world. Monographs include a variety of tests and may include an LC method for quantitative or qualitative purposes. Many such LC methods tend to be based upon ‘traditional’ column formats and technology such as 250 x 4.6 mm 10 μm porous particles. Recognising the recent advances in LC technology (smaller particles and smaller column formats) including the widespread use of solid core technology, an update of USP <621> (general chapter on chromatography) came into effect in 2014. This short article highlights the key features and gives an overview of the major changes to USP <621>. Improved productivity and solvent cost savings are demonstrated by applying the constant column length to particle size ratio option for method translations to example USP monographs using both porous and solid core particle based columns.

Introduction
Compendial and product specific testing is necessary within the pharmaceutical industry and independent testing laboratories to ensure the safety and quality of medicines produced by a variety of manufacturers for countries around the world. LC methods within monographs are common and used for a variety of quantitative and qualitative tests such as potency, purity and identification. Most pharmacopeia contain a general chapter on chromatography outlining broad guidance for performing LC methods listed within monographs. USP <621> describes general chromatography information for USP based procedures and includes the allowable changes to LC methods within USP monographs without revalidation [1]. The recent update to USP <621> came into effect on August 1st 2014 and describes new options for allowed changes to LC methods for analysts seeking to utilise modern rapid column formats that include smaller column dimensions, smaller particles and solid core technology. Considerable increases in productivity through reduced analysis times are therefore possible. Substantial reductions in solvent consumption are also possible with these new rapid column format, translated methods, highlighting further attractive cost savings. In this work, the new USP <621> guidance for translating LC methods to small dimension, rapid analysis format columns containing both porous and solid core particles is reported.

Experimental
Chemicals, reagents, analytes, solvents and water were purchased from Sigma-Aldrich (Poole, UK) and were suitable grade for LC separations. All analyses were performed on either Agilent 1100 or 1200 series LC instruments. ACE Excel and ACE UltraCore columns were provided by Advanced Chromatography Technologies Ltd (Aberdeen, UK) and are all commercially available formats.

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