Method development drug purity analysis

The purity was lower than desirable for NMR analysis, so further purification was undertaken to facilitate structure elucidation by NMR. The existing analytical methodology contained perchloric acid that was not suitable for preparative HPLC isolation and LC/MS analysis because of safety concerns with concentration of perchloric acid and high probability of damage to the mass spectrometer over time. A mass spectrometry compatible method using a 0.1% acetic acid buffer was selected as a starting point. Minor method development produced a suitable method to separate the reaction components the drug substance, the sulfoxide, and the N-oxide. 

The development of new separation methods for the analysis of drugs is continuously requested during drug design, development, production, and use. In this regard, some analytical issues are of particular importance, including purity assessment, analysis of isomers, detection of impurities, and/or related compounds. Although most of the methods used for pharmaceutical analysis involve... 

Selectivity is evaluated by analyzing the blank matrix and commonly used drugs and/or metabolites under the same conditions as developed for the analysis of the drug. Reproducibility in migration times is essential to evaluate the selectivity of the method. As peak width depends on the injected amount, the effects of sample overload must be investigated. Another way to validate the specificity is to assess peak purity using diode array or MS detection. 

In Table 1, the typical validation parameters required for the different types of analytical procedures are listed. For all these analytical procedures CE might be an appropriate analytical technique. In fact numerous validated CE methods for pharmaceutical analysis have been described in literature during the last decade.In Table 2, an overview is listed of the ICH validation parameters included in several reported CE validation studies. Since chiral purity determination is an important application area of CE methods, this test is listed separately as a specific analytical procedure. In addition, the determination of drug counterions has been included as a separate application. This overview illustrates that in general the required validation parameters are addressed in reported CE validation studies. It should be noted, however, that the validation parameters included in Table 2 are not necessarily evaluated exactly according ICH requirements in the reported references. Many pharmaceutical companies apply a phase-related validation approach in which the depth of validation depends on the clinical phase of development of the product involved. 

Agbaba et al. [56] developed an HPTLC method for the determination of omeprazole, pantoprazole, and their impurities omeprazole sulfone and N-methylpantoprazole in pharmaceutical. The mobile phase chloroform-2-propanol 25% ammonia-acetonitrile (10.8 1.2 0.3 4), enables good resolution of large excesses of the drugs from the possible impurities. Regression coefficients (r > 0.998), recovery (90.7-120.0%), and detection limit (0.025-0.05%) were validated and found to be satisfactory. The method is convenient for quantitative analysis and purity control of the compounds. 

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