Robustness related substances

The monograph of levocarbastine has already been revised. The determination of the related substances is performed by means of MEKC using an electrolyte solution composed of sodium dodecyl sulfate as a micelle-forming agent in addition to hydroxypropyl-/ -cyclodextrin in a boric acid buffer of pH 9.0. Due to the very good specificity and robustness the method is able to baseline separate the nine specified and detectable impurities and the drug substance. It is easy to meet the system suitability (Rs>4) the resolution between levocarbastine and impurity D was found to be 6.4 and the content of related substances less than 0.5% (see Figure lA and B). 

Other Considerations. Typically, the variations in robustness results are compared to the intermediate precision results to demonstrate that robustness is not affected significantly within normal day-to-day variation. When the related substance results are affected by some critical experimental parameters, a precautionary statement needs to be included in the procedure to ensure that this parameter is tightly controlled between experiments. For example, if percent organic of mobile phase affects the results significantly, the procedure should indicate the acceptable range for percent organic (e.g., 50% organic 2%)... 

Robustness for HPLC Analysis. The investigation of the effect of column, mobile phase, HPLC solution stability, and wavelength is performed in a manner similar to the HPLC potency/related substance assay. For solution stability, the... 

A. Karlsson, M. Berglin, and C. Charron, Robustness of the chromatographic separation of alprenolol and related substances using a silica-based stationary phase and selective retention of metoprolol and related substances on a porous graphitic carbon stationary phase, J. Chromatogr. A 797 (1998), 75-82. 

As illustrated by several examples, experimental design methods proved to be very useful in the development of reproducible and robust CE methods for the analysis of related substances in drugs. This includes the analysis of complex mixtures of substances isolated from natural sources and the simultaneous separation of chiral and achiral impurities as well as compounds with multiple... 

Prior to developing an HPLC method, its intended use must be carefully considered. For example, if the analysis is required to obtain an approximate value for the amount of candidate drug, such as for a solubility experiment, a crude method may be acceptable. Alternatively, if the HPLC method is to separate and determine related substances, i.e., synthesis intermediates and degradation products, from the compound of interest, a more robust method will have to be developed. Other considerations will include the amount of compound to be determined, from what type of matrix (e.g., formulation, reaction mixture, drug substance) and the number of and how quickly analyses are to be performed. 

THE FACTORS AND THEIR LEVELS. EXAMINED IN THE ROBUSTNESS TEST OF (82) ON A CHROMATOGRAPHIC METHOD FOR THE SEPARATION AND ASSAY OF A DRUG SUBSTANCE AND TWO RELATED COMPOUNDS IN TABLETS... 

The structure of DNA, an abbreviation for d eoxyriho n ucleic a cid, illustrates a basic principle common to all biomolecules the intimate relation between structure and function. The remarkable properties of this chemical substance allow it to function as a very efficient and robust vehicle for storing information. We begin with an examination of the covalent structure of DNA and its extension into three dimensions. 

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