Estimation of impurity profiles of drugs and related materials

Chemical and analytical characterization of related organic impurities in drugs

“…Impurity 18 in the same synthesis is the acetoacetate. Enol acetates 19 and 20 are the Z and E 3′-acetoxy-2′-butenoates of the 17-OH group [30,33,41], that is, side products of the acetylation of the intermediate 18.…”

“…3 shows, the main reaction is the formation of the 4-ene-3β-hydroxy derivative but some 4-ene-3α-hydroxy derivative 22 is also formed as an impurity of the intermediate ethynodiol leading to the formation of the epimeric 858 Fig. 6 Scheme for the formation of some impurities in norethisterone and norgestrel impurity 23 in ethynodiol diacetate [30,41,58]. Stereospecific hydroxylation by fermentation at C-11 leading to the 11β-hydroxy derivative is the key step in the synthesis of hydrocortisone (and prednisolone).…”

“…If TLC is used, reflection UV spectra are similarly easily available [9]. Although UV spectroscopy is the least effective among the spectroscopic techniques, often very important information is obtainable for the structure elucidation [17,34,36,37,41,43,44,45,46,47,49,58,65,66,69,70].…”

“…The following on-line techniques of GC-MS [18,36,37,46,52,57] and HPLC-MS are more developed. The latter is in our time the most generally used hyphenated method in impurity profiling [19,37,41,46,65,71]. The importance of CE-MS [12] and CEC-MS [20] is increasing.…”

“…If NMR spectroscopy [16,30,33,35,36,37,41,43,44,46,47,48,49,52,55,56,63] is also necessary for the structure elucidation, somewhat larger sample size is necessary. These samples are usually obtained by semi-preparative HPLC [21].…”