ESTIMATION OF IMPURITY PROFILES OF DRUGS AND RELATED MATERIALS .16. IDENTIFICATION OF THE SIDE-PRODUCTS OF THE ETHINYLATION STEP IN THE SYNTHESIS OF CONTRACEPTIVE GESTOGENS

A new apolar impurity (3,17 alpha-diethinyl-13-ethyl-3,5-gonadiene-17- ol, IIb) was detected and identified in norgestrel with the aid of thi n-layer and high-performance chromatography and spectroscopic techniqu es. IIb is the product of the acid-catalysed dehydration of an overeth inylated side product (Ib) of the ethinylation step in the synthesis o f norgestrel. IIb can be determined by thin-layer densitometry and hig h-performance liquid chromatography. Another impurity (17 alpha-ethiny l-13-ethyl-4-gonene-17-ol, IV), originating from a side product of the Birch reduction step in the synthesis of norgestrel was also detected and identified. The spot of IV overlaps with that of IIb in the TLC s ystem of USP XXIII but can be separated and quantificated by more sele ctive TLC systems and by gas chromatograpy. (C) 1997 Elsevier Science B.V.