High-performance liquid chromatographic separation and identification of epimeric 17-ketone impurities in commercial sample of dexamethasone sodium phosphate

Quantitative TLC Determination of Epimeric Ratios of 16-Methyl 17-Ketone Oxidation Products of Dexamethasone and Related Drugs

“…The densitogram of the epimeric impurity from the drug sample was compared with a chromatogram obtained from HPLC examination of another sample of the epimeric impurity extracted from the same batch of the commercial dexamethasone phosphate disodium solution for injection. The sample of the epimeric impurity and its high-performance liquid chromatogram were provided by the authors of the HPLC study (11). This qualitative work (11) included studies on the photographic methods of documentation conducted on concocted mixtures of the synthesized epimers (IIa and IIP) and on the natural epimeric impurity (IIa and IIB)…”

“…In addition, a massive contamination (50%) by the a-and P-epimers of this ketone (IIa and IIB) was reported (11) in a commercial sample of dexamethasone sodium phosphate (I) solution for injection. In that study (ll), it was found by HPLC that this 17-keto oxidation product was actually an epimeric mixture of the 16a-and 16a-methyl compounds and that the a to , B ratio could be determined approximately.…”

“…In that study (ll), it was found by HPLC that this 17-keto oxidation product was actually an epimeric mixture of the 16a-and 16a-methyl compounds and that the a to , B ratio could be determined approximately. Identification of the 16methyl 17-ketone epimers (IIa and Up) by TLC systems similar in nature to the reversed-phase HPLC system was attempted, but the TLC systems failed to separate the a-and 8-epimers; dexamethasone acetate, a related compound, consistently exhibited the same Rf value as the epimers (11).…”

“…An overview of possible physiological effects of such contamination, including references, was given previously (11). The aim of the present work was to develop a TLC technique that allows identification of epimeric 16-methyl 17-ketones (Ira and IIP) in samples of drugs related to dexamethasone.…”

“…Interest has developed in qualitative and quantitative studies of these epimeric C20 oxidation products by highperformance liquid chromatography (HPLC) (11) and TLC (12) because of their presence as impurities in dexamethasone (11)(12)(13) and dexamethasone sodium phosphate (I) drug samples. Inherently, the Cz2 steroids and their 17-0x0 derivatives possess a structural feature not exhib-ited by the C19 and Czl steroids and their oxygenated derivatives, namely, an optical center resulting from the additional methyl group at the C-16 position.…”