Purity, absolute

Specifications and Standards. Typical specifications for phthahc anhydride are given in Table 10. AH specifications are measures of purity. Sohdification point is a sensitive indicator of absolute purity, and is a key specification. Another key specification is molten color stabiUty, which is the color after being held at 250°C for two hours. This test ensures acceptable color after shipment in molten form and detects the presence of impurities that can cause discoloration at elevated temperatures. Phthahc acid level is a monitor of how well moisture has been excluded during storage and shipment. 

For purposes of dosage, the specific activity of an enzyme is usually expressed as International Units (lU) rather than in terms of weight. However, unit measurements do not provide information on the absolute purity of a given product. Moreover, purity is not as critical an attribute for oral enzymes, as opposed to those adrninistered parenteraHy, inasmuch as the gastrointestinal tract is capable of disposing of most inert contaminants. 

The important question, then, is not whether a substance is pure but whether a given sample is sufficiently pure for some intended purpose. That is, are the contaminants likely to interfere in the process or measurement that is to be studied. By suitable manipulation it is often possible to reduce levels of impurities to acceptable limits, but absolute purity is an ideal which, no matter how closely approached, can never be attained. A negative physical or chemical test indicates only that the amount of an impurity in a substance lies below a certain sensitivity level no test can demonstrate that a specified impurity is entirely al ent. 

This terpene occurs principally in oil of savin, but has also been found in marjoram, cardamom, sho-gyu and a few other essential oils. It is obtained from the fraction of oil of savin which boils below 195°, which amounts to about 30 per cent, of the oil. It has probably not been isolated in a state of absolute purity, but its characters are approximately as follows —... 

The acetic esters of the two santalols have been prepared, but their absolute purity has not been substantiated. 

In order to obtain nearly absolute purity of the spectra of these xanthophylls, it was necessary to calculate the difference Raman spectra. Therefore, for zeaxanthin, two spectra of samples, one containing violaxanthin and the other enriched in zeaxanthin, were measured at 514.5 nm excitation. After their normalization using chlorophyll a bands at 1354 or 1389 cm-1, a deepoxidized-minus-epoxidized difference spectrum has for the first time been calculated to produce a pure resonance Raman spectrum of zeaxanthin in vivo (Figure 7.10b). A similar procedure was used for the calculation of the pure spectrum for violaxanthin. The only difference is that the 488.0nm excitation wavelength and epoxidized-minus-deepoxidized order of spectra have been applied in the calculation. The spectra produced using this approach have remarkable similarity to the spectra of xanthophyll cycle carotenoids in pure solvents (Ruban et al., 2001). The v, peaks of violaxanthin and zeaxanthin spectra are 7 cm 1 apart and in correspondence to the maxima of this band for isolated zeaxanthin and violaxanthin, respectively. The v3 band for zeaxanthin is positioned at 1003 cm-1, while the one for violaxanthin is upshifted toward 1006 cm-1. 

When a compound is observed to melt without decomposition, DSC analysis can be used to determine the absolute purity [44]. This method can therefore be used to evaluate the absolute purity of a given compound without reference to a standard, with purities being obtained in terms of mole percent. Unfortunately, the method is limited to reasonably pure compounds that melt without decomposition, since the assumptions justifying the methodology fail when the compound purity is below approximately 97 mole%. 

It is, however, pertinent to mention here that pharmaceutical chemicals must maintain a very high degree of chemical purity. It is quite obvious that a state of absolute purity may not be achievable, but a sincere effort must be exercised to obtain the maximum freedom from foreign substances. Bearing in mind the exorbitant operational costs to attain the highest standards of purity, perhaps some of these processes are not economically viable. Therefore, a compromise has got to be made to strike a balance between the purity of a substance at a reasonably viable cost and at the same time its purity e.g.. being fully acceptable for all pharmaceutical usages. 

Unfortunately, many reactions do not occur with quantitative conversion and in near absolute purity. The work-up and purification of most chemical processes probably takes up most of a bench chemists time. Therefore techniques that simplify and accelerate these operations not only free up valuable time, but allow greater creativity and increased levels of output. Here again, supported systems can be used to aid the chemist in the guise of scavengers, quenching agents and catch and release systems. 

Since procaine hydrochloride melts without decomposition, the DSC method can be used to establish the absolute purity of the material. The DSC purity of the tested sample was found to be 100.14 mole%, and the enthalpy of fusion for this sample was determined to be 31.5 kJ/mole (7.52 Kcal/mole). 

In recent years researchers both in the U.S.A. and Europe have expended considerable time and effort in seeking to prepare rare earth metals of very high purity. For the most part their work has been successful and today it is possible to obtain several metals having an absolute purity of 99.99%. Understandably such metals tend to be available only in small quantities and their true cost of preparation is often discounted when set against a particular requirement. 

Absolute purity cannot be achieved for any material, but high purity can and it is generally desirable and often mandatory for the applications intended for solvents. Commercially available solvents can be obtained in several categories of purity and the desired or required purity depends on the envisaged application. It is, therefore, impractical to specify a solvent that is pure for all possible applications. 

Overlooking the anomalies due to the lack of absolute purity of the reagents, one must assign a zero reaction order with respect to aluminum-alkyl concentration, in the range of the above reported conditions. 

The crystal mass is then separated from the mother liquor by careful decantation or by filtration through a Buchner funnel. In either case, the product is carefully washed several times with cold distilled water, f then with 95 per cent ethyl alcohol and with ether. If the crystals are washed by decantation, the yield may not exceed 75 per cent. If absolute purity is not essential, and filtration is carried out on the Buchner funnel, the yield may be considerably higher as indicated by the following experimental results. 

Where absolute purity is not necessary, hard rubber ware may be substituted for platinum. 

Hydrolysis in aqueous solution precipitates hydrated titanium dioxide which, after washing and drying, can be calcined at 800°C to remove water and residual Cl. This method has been the basis of producing titanium dioxide of 99.999% purity. If retaining a high specific surface area is important, it may be convenient to reduce the residual Cl content by Sohxlet extraction rather than calcination. For many electroceramic uses, the millability of the product is as important as the absolute purity. A number of process variants designed to modify particulate morphology have been described (67). 

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... 

As discussed in some detail on p. 202 of this review, the enantiomers (-)-HU-210 (which retains the stereochemistry present in THC) and (+)-HU-211 were originally prepared in order to establish whether the activity of the cannabinoids is stereospecific. The synthetic path is shown in Figure 5.2 [25], The intermediate ketones (5 and enantiomer) can be easily crystallized to absolute purity and therefore the final products HU-210 (3) and HU-211 (4) are obtained with e.e. higher than 98.8%. This was a central aim of our synthetic approach in order to make possible the eventual therapeutic use of the [35,4S] enantiomer (4), as the presence of traces of the highly psychotropic [3/J, 4/ ] enantiomer (3) could lead to undesirable side-effects. The enantiomeric purity of thrice recrystallized (3) and (4) was established by h.p.l.c. analysis of the diastereoisomeric bis(MIPA) esters obtained by reaction with (S)-(+)-a-methoxy-a-(trifluoromethyl)phenylacetyl (MTPA) chloride. As expected, we found that HU-211 (4) has no cannabimimetic activity [20-24], However, unexpectedly, we observed that it exhibits pharmacologi-... 

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