Purity, analysis

When using continuous DSC for purity determination, the data must be corrected for instrument lag and F must be corrected for the omitted portion E as shown in Fig. 4.42 for testosterone. Computer programs exist to optimize the fit to a linear curve. Over-correction would give a downward deviation instead of the upward deviation. This purity determination is only applicable if there is solubility of A and B in the melt, but no solubility of B in crystals of A (eutectic system). 

---

Fig. 2. An SPC control chart of the purity analysis of a reference standard where (—) represents the average value and UCL and LCL are the upper and...

Purity analysis and characterization of the test substance should be performed for each lot. A retention sample from each batch of the test substance should be archived. All unused test substance and partially empty containers should be retained until the final report is signed, unless a prior waiver has been obtained from the EPA. 

A study of the nomenclature problem indicates that only samples are analyzed elements, ions, and compounds are identified or determined. The difficulty occurs when the sample is nominally an element or compound (of unknown purity). Analysis of... (an element or compound) must be understood to mean the identification or determination of impurities. When the intent is to determine how much of such a sample is the material indicated by the name, assay is the proper word. ... 

One concern relating to SDS-PAGE-based purity analysis is that contaminants of the same molecular mass as the product will go undetected as they will co-migrate with it. Two-dimensional electrophoretic analysis would overcome this eventuality in most instances. 

A number of CZE applications exist for the separation of proteins and other molecules in purity analysis, structural studies, binding and equilibrium determinations, in-process product analysis, and mobility measurements. The following applications illustrate the use of CZE for both research and routine QC analysis. 

As RP-HPLC is the method of choice for purity analysis, it provides a namral starting point for the selectivity scouting. The approach described here for RP-HPLC is directly applicable to NP, chiral, and other chromatography modes. Figure 7.3 provides examples for stationary and mobile phases providing a starting point for the screening exercise. 

Gel electrophoresis and, more recently, CGE have been employed principally in molecular biology and biochemical science for the separation of macromolecules such as proteins and nucleic acids. And GCE has been successfully used in oligonucleotide purity analysis, antisense gene therapy, DNA sequencing, PCR product analysis, and DNA forensics. 

The optical purity of the CDA determines the limit up to which optical purity analysis can be made from the enantiomeric mixture of the chiral analyte. Consequently, reliable data... 

This technique is a variant of CZE. A cationic or anionic surfactant compound, such as sodium dodecylsulphate, is added to the mobile phase to form charged micelles. These small spherical species, whose core is essentially immiscible with the solution, trap neutral compounds efficiently by hydrophylic/hydrophobic affinity interactions (Fig. 8.7). Using this type of electrophoresis, optical purity analysis can be conducted by adding cyclodextrins instead of micelles to the electrolyte. This is useful for separating molecules that are not otherwise separable. Under such conditions, the enantiomers form inclusion complexes of different stability with cyclodextrin (cf. 3.6). 

In the case of purity analysis or the measurement of major components, the traceability steps and associated uncertainties illustrated in Fig. 3 can be expected. In these cases, a small uncertainty is normally required and a variety of factors can contribute significantly to it, including mass, volume, and other physical as well as chemical effects. Thus in these cases, both Ur and Uc may be significant. 

NRCCRM, China has establish many kinds of authorized measurement methods, solved the problem of purity analysis, and completed research on several sets of primary reference gases. 

The purity analysis of a recombinant produced product is difficult because the accuracy of protein purity is method-dependent and is influenced by the shortcomings of the analytical procedures (Chapter 2). Proteins are highly complex molecules therefore, it is generally very desirable to utilize more than one method to define a given protein s purity. To assure the purity of... 

An important fact inherent in the purity analysis of a recombinant pharmaceutical is that the absolute purity of any protein is an elusive, if not an unobtainable, measurement. For biopharmaceuticals, purity is a relative term. Protein purity is method-dependent and is defined by the shortcomings of the analytical procedure. Also, unlike small traditional drugs, proteins are highly complex molecules. For these two reasons, more than one method must be utilized to define a protein s purity. The greater the number of methods used in the purity analysis, the greater the assurance is that the product is pure. Furthermore, the purity determined by an analytical method can only be properly interpreted based on the method s validation. Analytical methods validation is critical to and inseparable from purity determinations. A detailed discussion on analytical methods validation is beyond the scope of this chapter but other sources of information are available for the interested reader.11 13... 

The key properties of our ion channel library, namely molecular weight, polar surface area, clogP, and number of hydrogen bond acceptors and donors, are within the lead-like range of compounds (Figure 8.14) [59]. A purity analysis of a small... 

An interesting feature of this study is the enantiomeric purity analysis of the products. By converting the amine functionality of the pyrrolidine to a 3,5-dinitrobenzamide, the substrate can be analyzed by chiral HPLC. To date, the 3,5-dinitrobenzamide of 2-substituted pyrrolidines that the submitters have prepared have beer baseline-resolved by the Pirkle S-N1 N-Naphthylleucine column. This approach obviates the need for MPTA-derivativization which has been previously employed in enantiomeric purity determinations.3 5... 

The use of UV-vis and FT-IR spectroscopy in determining drug impurities without previous chromatographic separation is limited because of the low selectivity of both methods. In some cases, when the impurity has spectral properties that are very different from those of the active substance, the direct measurement of absorbance can give some useful data about the structure of the impurity. But, in many cases the impurity has a similar structure to the active substance and, therefore, their UV and IR absorption spectra are similar, and overlap with each other additively. This means that direct use of spectroscopic methods in drug purity analysis is limited [49]. 

Selectivity of the UV method can be increased by the use of spectra derivatives [50]. Derivative spectrophotometry is a chemometric method in which classic UV spectra (zero-order spectra) are differentiated with respect to wavelength before being analyzed. It is much more selective and precise than classic UV spectroscopy [50]. Examples of the use of the spectra derivatives method in drug purity analysis are shown in Table 8.4. 

---