Barbiturates, non-nitrogen substituted European Pharmacopoeia

The various barbiturates and thiobarbiturates (hereafter barbiturates) are different primarily in their alkyl or aryl substituents at the five position. At present less than monographs reference barbiturates, non-nitrogen substituted, all of them describing pharmacologically active barbiturates. 

A test first described by Parri in 1924 in which the barbiturate gives a colored complex with cobalt(II) has been adapted by the pharmacopoeia. The test parameters of the determination have been modified several times through the years, but the presence of a number of elements constitutes the essence of the procedure a ion, normally cobalt(II) or copper(II) an organic solvent, preferably one with a Lewis base character and an alkaline reaction and the absence of water in the test solution. Furthermore ammonia, or an organic amine, is sometimes added. 

Several organic solvents have been suggested for the procedure, but methanol and alcohol are among the most widely used. This is most likely because it has a relatively strong Lewis base and therefore has a strong 

A test solution is prepared by dissolving about 5 mg of the substance to be examined in 3 ml of methanol R. A 0.1 ml solution containing 100 g/1 of cobalt nitrate R and 100 g/1 of calcium chloride R is added. After mixing, 0.1-ml of dilute sodium hydroxide solution R is added with shaking. A violet-blue color and precipitate are formed. 

In the variant of the procedure adapted by the European Pharmacopoeia, no amine ligand is added. Instead, calcium is added, and this gives a variant of the above complexes of a structure, which has not been elucidated. The complex is insoluble in methanol. The presence of calcium also explains the violet-blue color, since most of the complexes with amines are violet. The cobalt complexes are more likely to precipitate when making the test solution 

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