Impurities in a morphine sulfate drug product identified as 5-(hydroxymethyl)-2-furfural, 10-hydroxymorphine and 10-oxomorphine.

Abstract:

:Stability testing of morphine sulfate formulated with nonpareil sugar seeds (consisting of sucrose and starch) and fumaric acid revealed the formation of the three impurities 5-(hydroxymethyl)-2-furfural, 10-hydroxymorphine and 10-oxomorphine. 5-(Hydroxymethyl)-2-furfural was isolated via semipreparative HPLC utilizing volatile mobile phase constituents and was identified by analysis of its HRMS and NMR spectra. 10-Hydroxymorphine and 10-oxomorphine were obtained via semipreparative HPLC and subsequent removal of ion-pair reagents using an anion exchange resin, or by solid phase extraction, and identified by spectroscopic analysis followed by comparison with authentic materials. 5-(Hydroxymethyl)-2-furfural is a degradation product of hexose sugars, and its formation in the presence of morphine sulfate formulated with fumaric acid suggests that caution should be exercised when including nonpareil seeds in formulations that contain acidic drug salts and/or acid excipients. The preliminary results of tests on the interaction of acidic salts of some other drugs with nonpareil seeds are presented.

journal_name

J Pharm Sci

authors

Kelly SS,Glynn PM,Madden SJ,Grayson DH

doi

10.1002/jps.10330

subject

Has Abstract

pub_date

2003-03-01 00:00:00

pages

485-93

issue

3

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(16)31205-9

journal_volume

92

pub_type

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