Compound purity

The schools of thought on compound purity are many and various. They range from the I do not care through to 90 % minimum purity. The average requirement would be somewhere in excess of 80 % for purchases from compound vendors. Here it is a cost factor that applies The purer the compound must be, the higher the price. Interestingly, the purity standard expected from a compound vendor is often higher than the company internal standard, especially when the compounds are from combinatorial chemistry. 

Compound purity is a real issue for stfucture-activity correlations, which become more and more important in discovering drugs. For this reason alone, purity is something to invest in because quality saves time. The label on the bottle should say something meaningful about the compound inside. If the compound is more than 90 % pure, it should also be the right compound The combination of H NMR and LC-MS is now an accepted standard in quality control for compound libraries. Also of note is the current trend for many 

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The temperature of explosive decomposition of trinitrotoluene very much depends on the compound purity. The table below shows the influence of various impurities on this compound. 

BCR Analytical Approach for the Certification of PAHs in Natural Matrix CRMs Prior to the certification analyses for the CRM, each participating laboratory has to prepare standard solutions of the analytes to be determined from certified reference compounds (purity >99.0 %) to calibrate their instruments for response and response linearity (multiple point calibration), detection limit, and reproducibility. In the case of PAH measurements, reference compounds of certified purity are used as internal standards, which are not present at a detectable concentration in the matrix to be analyzed (e.g. indeno[i,2,3-cd]fluoranthene (CRM 267), 5-methylchrysene (CRM 081R), benzo[f ]chry-sene (CRM 046), picene (CRM 168), and/or phenanthrene-dio). 

A piperidene-based intermediate was found to crystallize as either an anhydrate or a hydrate, but the impurity profile of the crystallized solids differed substantially [26], Considerations of molecular packing led to the deduction that there was more void volume in the anhydrate crystal structure than in that of the hydrate form, thereby facilitating more clathration in the anhydrate than in the hydrate phase. This phenomenon was led to a decision to crystallize the hydrate form, since lower levels of the undesired impurity could be occluded and greater compound purity could be achieved in the crystallization step. 

The sample temperature is increased in a linear fashion, while the property in question is evaluated on a continuous basis. These methods are used to characterize compound purity, polymorphism, solvation, degradation, and excipient compatibility [41], Thermal analysis methods are normally used to monitor endothermic processes (melting, boiling, sublimation, vaporization, desolvation, solid-solid phase transitions, and chemical degradation) as well as exothermic processes (crystallization and oxidative decomposition). Thermal methods can be extremely useful in preformulation studies, since the carefully planned studies can be used to indicate the existence of possible drug-excipient interactions in a prototype formulation [7]. 

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%. 

Thermal methods have found extensive use in the past as part of a program of preformulation studies, since carefully planned work can be used to indicate the existence of possible drug-excipient interactions in a prototype formulation [2], It should be noted, however, that the use of differential scanning calorimetry (DSC) for such work is less in vogue than it used to be. Nevertheless, in appropriately designed applications, thermal methods of analysis can be used to evaluate compound purity,... 

Compound purity or integrity testing using methods such as UV absorbance, evaporative light scattering, MS, NMR, etc.25... 

Compound purity (or integrity testing) is important to ensure purity in the early stages because erroneous activity or toxicity results may be obtained by impure compounds, ft is initiated during hit identification and continued into lead and candidate selection. 

Zinc-containing complexes have applications in many areas. The monitoring of compound purity, degradation or modification during different processes is sometimes crucial for the success of the endeavor. Mass spectrometry has become a common tool for prompt analysis and has been applied to investigations involving a variety of Zn-containing species. ... 

TFP (tetrafluorophenol) esters55 in a 96-well filter plate, encapsulated in a Calypso frame assembly. Final compound purities were improved (13% on average) by the addition of PS-NCO. 

Intimately connected with preparative LC is the development of synthetic compounds that are either new or identical to those found naturally. The capability that HPLC added to synthesis procedures—the ability to verify compound purity, separate stereoisomers, and confirm compound identity— was utilized in the syntheses ofvvitamin Bj2 and oligonucleotides, and in natural product isolation. These areas are discussed in Chapter 2. 

High level compound purity is essential for a hit to become a genuine lead. For example, the terpene, ursolic acid, has shown inconsistent biological activity across a number of diverse assays. Recently, purity-activity studies of its antimycobacterial activity were performed using ursolic acid samples of varying purity. Ursolic acid showed enhanced antimycobacterial activity when impure.43... 

Elements and inorganic compounds Purity 99.9% minimum for the preparation of aqueous standard solutions as described in Section IV.A.2. 

Powers et al. (82) reported the synthesis of a 1280-member library of discrete chalcones in solution (L4, Fig. 8.16) with an extremely high (96% average) compound purity. This library was used as such or through subsets to generate several primary libraries as sources of novel biologically active compounds. A 25,600-member hbrary... 

More often, as described earlier, compound purity is reported taking into account the purities determined from the UV, ELSD, and CLND detectors. In some instances, purity assessment has been made based on the intensity of the expected ion in the mass spectrum relative to the sum of the intensities of all ions in the spectrum. This method, however, is only a very crude estimate of purity, because ionization efficiencies for compounds can vary widely within and between classes of compounds. Though LC/MS (with UV and/or ELSD detection) has been adopted as the method of choice for assessing the quality and quantity of material prepared by parallel synthesis techniques, a decision still needs to be made by each respective organization as to what constitutes acceptable quality before submitting a sample for biological testing. 

The molecular formula of a molecule can also be defined by high resolution mass spectrometry (hrms). The observed mass for the molecular ion or pseudo molecular ion must normally be within 5ppm of the calculated mass for El (electron impact) measurements, or within lOppm for Cl (chemical ionization) measurements. It is important to note that high resolution mass spectrometry confirms that some molecules of a particular molecular formula are present in the sample, but does not give any indication of purity. Some other evidence of compound purity will therefore be required. 

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