Purity assignment

In most cases, the purity of a pharmaceutical substance is determined by comparison of the reference standard with the known purity assigned. On the other hand, when no reference standard sample is available, the purity is determined by an absolute method in which the calculated result is based on theory and not by a comparative method. Purity established by analytical methods such as phase-solubility analysis or differential scanning calorimetry (DSC) is known as absolute purity (Figs. 3 and 4). 

In a patent assigned to Mitsubishi, air oxidation is carried out in the presence of copper salts to avoid the formation of complicating impurities in the oxidation of dihydrovitarnin to vitamin (33). In other work, high yields of vitamin were obtained by performing the oxidation in an alkaU medium (34). High purity vitamin can also be obtained by an oxidation in dimethyl sulfoxide (35). 

Two distinct sesquiterpenes exist in the essential oil of Santalum album, known as a-santalene and /3-santalene. 8-santalene is probably a bicyclic and a-santalene a tricyclic sesquiterpene. These sesquiterpenes were discovered by Guerbet. From the method of their preparation it is doubtful whether they have been obtained in a state of purity, so that the characters assigned to them must be accepted with some reserve, and as probably being only approximate. 

Structure of Oxy-F Compound F is extremely unstable and is difficult to obtain at a level of purity suitable for NMR studies. However, an oxidation product, Oxy-F, formed when F is left standing at — 20° C, is considerably more stable than F and can be purified to a sufficiently high level of purity. Oxy-F is nonfluorescent and shows absorption maxima at 237 nm and 275 nm (shoulder). The high-resolution FAB mass spectrum indicated the molecular formula of Oxy-F to be C33H3809N4Na2 [m/z 703.2363 (M + Na)+ and 681.2483 (M + H)"1"]. The H and 13C NMR data allowed the assignment of structure 7 to oxy-F (Fig. 3.2.6 Nakamura et al., 1988). 

Tables Assignment and wavenumbers (cm ) of the external and torsional vibrations of a-Ss based on polarization dependent studies [106, 107]. In the first two columns the type and symmetry classes of the molecular and crystal vibrations, respectively, are given. The wavenumbers of the vibrations are listed in the columns infrared and Raman corresponding to the order of symmetry species given in the second column (crystal). " S means orthorhombic Sg with natural isotopic composition, while stands for isotopically pure Sg crystals (purity >99.95%)... 

The proton magnetic resonance spectrum of the product in trifluoroacetic acid shows that the isomeric purity is greater than 90%. The proton magnetic resonance spectral properties for the isomeric amino ketones in both trifluoroacetic acid and chloroform-d are as follows (solvent) 8 (multiplicity, number of protons, assignment, coupling constant J in Hz.) 1-... 

Cycloamylose forms inclusion complexes stereoselectively with the enantiomers of isopropyl methylphosphinate (124) from which it was possible to isolate one enantiomer with an optical purity of 66%. The absolute configuration of menthyl methylphosphinate has been revised to the opposite of that previously assigned. 

Substances (impurities) which are not the subject of a monograph are usually synthesized or supplied by the manufacturer. In this case a purity in excess of 90.0 % is required provided that the reference substance is employed in a limit test. If the reference substance (impurity) is employed in a quantitative test then the purity requirement is normally better than 99.0 %. When it is less, then an assigned content must be established. 

Although not used for assay purposes, the purity of the CRS should be at least 90 %. However, when the substance is used in a quantitative test and the purity is not greater than 99 % a content will be assigned. 

For the mixtures described under (3) it is sufficient to determine the chromatographic profile of the CRS and to demonstrate that all impurities are well separated according to the monograph description. When the spiked sample is also used in the purity control, then the content of the impurity in the CRS material must be determined by appropriate chromatographic methods and a value assigned to the material. 

Analytical Methods. A Schimadzu Liquid Chromatograph was used to monitor the reaction conversion and to assign chemical and chiral purity to the final product. Structures were verified by HNMR spectra obtained on a Bruker (Model UltraShield 400 spectrometer). Optical rotations were measured on a Perkin Elmer Model 341 Polarimeter. 

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