Purity methods

The effects of size surface area, shape, purity method of synthesis, charge, surface coating, functionalized groups, and aggregation need to be carefully considered when assessing potential risks of CNT toxicity. Toxicology studies on CNTs should be accompanied by improved control in manufacturing and improved analysis before CNTs can be successfully used for pharmaceutical applications. 

Chiral or achiral assay and purity determinations are done according to an external calibration calculation procedure, either with or without internal standardization. The calibration is performed against a 10% w/w (compared to the nominal concentration of the sample solution at 100% w/w) reference standard solution. The sample solution for the purity determination remains at the 100% w/w level, while that of the assay determination is diluted 10 times. The reason for the difference in concentration levels is similar to the purity method. A suggested sample injection sequence can be... 

MS compatibility is not a must, but preferred. For achiral purity methods an alternative MS compatible, supportive method is available to support identification... 

TABLE 3 CE Purity Methods and Their Likelihood of Success... 

TABLE 9 Ways and Limitations to increase Sensitivity of a UV-Based CE Purity Method... 

Liu, L., Osborne, L. M., and Nussbaum, M. A. (1996). Development and validation of a combined potency assay and enantiomeric purity method for a chiral pharmaceutical compound using capillary electrophoresis. J. Chromatogr. A 745(1—2), 45 —52. 

Bullock, J. (1996). Capillary electrophoretic purity method for the novel metal chelator TMT-NCS.. Pharm. Biomed. Anal. 14, 845-854. 

CE as a technology is not well adapted for fraction collection, thus the classical spike accuracy approach cannot be followed for CE-based purity methods. However, recovery may be evaluated through a sample recovery study by dilution, which must be assessed using a minimum of nine determinations over a minimum of three concentration levels covering the specified range. If one applies 15 determinations over five concentration levels covering the range, the data can be used as both accuracy and linearity. 

Methods 1 and 2 are intended to control the boiler water pH and to precipitate the calcium and magnesium compounds as a flocculenl sludge, so that they can be removed in the boiler blowdown rather than being deposited on heat-transfer surfaces. Method 1 maintains an excess of hydroxide alkalinity. The effects of alkalinity are discussed later under Steam Purity. Method 3 involves the addition of a complex mctal-chelant compound such as ethylenediainine-tetraacetic acid i a.(FDTA) or niirilolriacelic acid (NTA). In Method 4, as ihe name implies, no solid chemicals are added to the boiler or pre-boiler cycle. The pH of the boiler water and condensate cycle is controlled by adding a volatile amine. 

Test A The Rf value of the principal spot observed in the chromatogram of the Identification solution corresponds to that of the principal spot observed in the chromatogram of the Standard solution containing 0.15 mg of USP Omeprazole RS per ml, obtained as directed in the test for Chromatographic purity, Method 1. 

Diphenyldramine Tablets HPLC Powder extracted with c8 phosphate, dibasic 0.0547(73 27) CHjCN-5 mM 258 nm 162 [4] GC [2,974] HPLC [3,975] Peak purity, methods [423]... 

CASE STUDY 3 HPLC PURITY METHOD DEVELOPMENT CHALLENGES FOR A FIXED COMBINATION PRODUCT CONTAINING A LOW-DOSE ACTIVE INGREDIENT AND A HIGH-DOSE ACTIVE INGREDIENT... 

Development of a Purity Method for a Fixed Combination Product... 

CASE STUDY 3 HPLC PURITY METHOD DEVELOPMENT CHALLENGES 251... 

TABLE 10.4 HPLC Chromatographic Conditions for the Fixed Combination Tablet Purity Method... 

The authors would like to thank Vincent Bobin for the solubility data for Compound A. The authors would also like to thank the following individuals for their work on Compound B described in this chapter Daniel Gierer for manufacture of the placebo tablets Amy Orce for her work on the extraneous syringe peak Thomas Sharp, George Horan, and Ronald Morris for their work on impurity identification and Cheryl Kirkman, Heidi O Donnell, Britt-Marie Otano, Doreathea Roberts, J. Sean Space, and Gregory Steeno for their work on the small volume dissolution method. In addition, the authors would like to thank Amanda Deal and Kelly Field for their work on the HPLC purity method development for the fixed combination tablet. 

As for HPLC purity methods, the determination of impurities in a sample of analyte is best done by a relative method comparing impurity peaks in sample solution chromatograms with impurity peaks in chromatograms from solutions of reference standards of impurities. Unfortunately, however, it is often the case that such reference standards are not available. Under these circumstances some approximations must be made. 

The basis of any calorimetric purity method is the relationship between the melting depression of a substance and the level of impurities according to van t Hoffs law. The purity is readily calculated from the DSC curve of a single melting event of a few milligrams of the substance, without the need for reference standard of the drug substance and its impurities. 

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