Solvent purity test

There are three aspects of the question of solvent purity that have to be considered the specification of the purity of the given solvent its further purification, if necessary and the testing of the actual purity of the original or purified solvent. 

Procedures for the Purification of Solvents 289 Tests for Purity of Solvents 291... 

Purity tests for salts are much more problematic than are purity tests for solvents. The only way to follow the salt purity rigorously is by careful element analysis by a combination of methods, which include atomic absorption, ICP (in solutions), and, to some extent, MS. Water contamination can be detected relatively easily by IR spectroscopy. All the above-mentioned salts have characteristic IR spectra in which the hydration water has specific bands. 

Information on solvent purification, purity tests and properties can be found in several reviews [14-20]. 

Purity tests—heavy metals, limits of methanol content, residual organic solvents, micro-organisms, mycotoxins, pesticides. 

The final validation test is done to demonstrate that no drug substance was lost from the extraction process, as this is a purity test. In a typical extraction process, as described above, the sample is crushed, extraction solvent is added, the sample is then stirred, sonicated, centrifuged, and filtered. In some cases, the drug substance will adhere to the filter. In this event, a study of numerous types of filters ensues to find one that yields 100% recovery. 

For each herbal drug preparation, a comprehensive specification must be submitted. This must be established on the basis of recent scientific data and must give particulars of the characteristics, identification tests, and purity tests. This has to be done, for example, by the appropriate chromatographic methods. If deemed necessary by the results of the analysis of the starting material, tests on microbiological quality, residues of pesticides, fumigation agents, solvents, and toxic metals have to be carried out. Radioactivity should be tested if there are reasons for concerns. Quantitative determination (assay) of markers or of substances with known therapeutic activity is required. The content must be indicated with the lowest possible tolerance. The test methods must be described in detail. 

In the two TLC systems mentioned above any aglycons present lie at the solvent front. For this reason an additional chromatographic system has been developed for purity testing and stability investigations. This employs prewashed and activated HPTLC plates. 

Purity test of a pharmaceutically active substance (top of the picture is the solvent front)... 

Figure 46. Effect of the presence of 1 % ammonia solution in the solvent system on the purity testing of dimenhydrinate according to the DAB (shots in 254-nm UV light)...

Many chemicals are available that can be used without further purification. Their selection is made on a trial and error basis, and even different lots from the same supplier may differ in purity. Volatile buffers and solvents such as pyridine, acetic acid, formic acid, and n-propanol, which are employed for chromatography, can be purified by distillation over ninhydrin. Constant-boiling hydrochloric acid is rountinely prepared over sodium dichromate (Schwabe and Catlin, 1974), and water of high purity is obtained from a system composed of a 0.2-fim particle filter, an activated charcoal cartridge, and two deionizer cartridges (Hydro Service and Supplies, Durham, North Carolina). The solvents are tested for purity in the following manner. A sample of the solvent is dried in vacuo. The residue is dissolved in pH 2.2 citrate buffer and injected onto the amino acid analyzer column. The distilled solvents are typically found to contain aspartic acid, serine, and glycine at 20-30 pmol/ml as the major contaminants. 

For the intermediates of synthesis, if the origin of the solvent is under eontrol (e.g., existence of contraets/Quality Assurance audits) a simplified monograph is eompletely adequate (see Table 14.21.1.5) as long as the supplier provides a detailed eertifieate of analysis where impurities (ineluding solvents) are properly speeified with aeeeptable limits. If the same solvent is used for the erystallization step additional purity tests are neeessary (Table 14.21.1.6). 

FreimuUer, S. Horsch, Ph. Andris, D. Zerbe, O. Altorfer, H. Formation mechanism of solvent induced artefact arising from chromatographic purity testing of -y-irradiated chloramphenicol. Chromatographia 2001, 53, 323-325. 

Various sulphonphthalein dyes which are used as acid-base indicators, e. g., th3nnol blue, bromophenol blue and phenol red, may be separated using solvents 11—13 (Table 131). Waldi [82] has determined the hB/-values of indicator dyes with a view to identification and purity testing he used standard conditions on alumina G-silica gel G [1 1) layers, with ethyl acetate-methanol-6N ammonium hydroxide solution (60 + 30 + 10). The time of run was 30 min. Results are in Table 132. 

For chromatographing protected, larger peptides (up to 10 amino acid units), Gttttmann [143] recommends silica gel or Alox layers and dimethyKormamide or acetic acid containing 5—10% water as solvents. Detection is with the chlorine-iodine reaction and jB/-values lie between 0.3 and 0.9. These are said to be not very reproducible but the method has been used successfully for purity testing. Schellenberg [144] recommends the solvents chloroform-acetone (90 + 10) and (80 + 20) cyclohexane-ethyl acetate (50 + 50) and chloroform-methanol (90 + 10). 

One of the best tests of purity of dioxane is the formation of the purple disodium benzophenone complex during reflux and its persistence on cooling. (Benzophenone is better than fluorenone for this purpose, and for the storing of the solvent.) [Carter, McClelland and Warhurst Trans Faraday Soc 56 343 I 960], TOXIC. 

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