Published:Journal of Chromatographic Science,
ISSN 0021-9665 Volume
47, Number 5, May/June 2009, pp. 378-386
Development and Validation of a Stability-Indicating
RP-HPLC Method for Assay of Alphamethylepoxide and Estimation
of its Related Compounds
Kang Ping Xiao, Fang Zhu Liu, Yuan Xiong, and
Abu M. Rustum
Global Quality Services–Analytical Sciences, Schering-Plough
Corporation, Union, NJ 07083
Alphamethylepoxide (16α-methyl-Δ1,4-pregnadiene-9β-11β-oxide-17α,21-diol-3,20-dione)
is a key intermediate for the synthesis of various active pharmaceutical
ingredients of steroid compounds. A stability-indicating reversed-phase
high-performance liquid chromatographic (RP-HPLC) method for
the assay of alphamethylepoxide and estimation of its related
compounds has been developed and validated. It can accurately
quantitate alphamethylepoxide in the presence of numerous structurally
related compounds (including the β-epimer, known as betamethylepoxide).
This method can also adequately separate most of the impurities
from each other and estimate their quantities in alphamethylepoxide
samples. The stability-indicating capability of this method has
been demonstrated by adequate separation of the degradation products
from alphamethylepoxide in stress degraded and aged stability
samples. A 15 cm × 4.6 mm i.d. ACE C18 HPLC
column is the primary column used in this method, and a 15 cm × 4.6
mm i.d. A Develosil ODS UG column serves as the alternative column.
The mobile phase consisted of 10mM sodium sulfate, 0.05% (v/v)
phosphoric acid, and acetonitrile. This method can accurately
assay the content of alphamethylepoxide (in a given lot) with
a % relative standard deviation of less than one. It can also
estimate individual impurities down to 0.05% level compared with
the alphamethylepoxide peak in the sample.
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