Journal of Pharmaceutical and Biomedical Analysis
20 (1999) 373–383
A comparison of gas – liquid chromatography, NMR
spectroscopy and Raman spectroscopy for determination of
the substituent content of general non-ionic cellulose ethers
C. Alvarez-Lorenzo
a
, R.A. Lorenzo-Ferreira
b
, J.L. Go ´ mez-Amoza
a
,
R. Martı ´nez-Pacheco
a
, C. Souto
a
, A. Concheiro
a,
*
a
Departamento de Farmacia y Tecnologı ´a Farmace ´utica, Facultad de Farmacia, Uniersidad de Santiago de Compostela,
15706 Santiago de Compostela, Spain
b
Departamento de Quı ´mica Analı ´tica, Nutricio ´n y Bromatologı ´a, Facultad de Quı ´mica, Uniersidad de Santiago de Compostela,
15706 Santiago de Compostela, Spain
Received 28 July 1998; received in revised form 27 October 1998; accepted 1 November 1998
Abstract
This paper describes and compares three techniques that can be used to characterize the substituent content of
hydroxypropylcellulose (HPC and L-HPC) and hydroxypropyl methylcellulose (HPMC): gas – liquid chromatography
(GLC) with a BP1 column and FI detection,
13
C-NMR spectroscopy of hydrolysed samples, and Raman spec-
troscopy. GLC and
13
C-NMR spectroscopy both allow independent quantification of hydroxypropoxyl and methoxyl
contents.
13
C-NMR spectroscopy, though requiring lengthier sample preparation, has the advantage of also
quantifying the degree of substitution at each substitutable glucopyranose hydroxyl. Raman spectroscopy may be
useful for rapid approximate estimation of hydroxypropoxyl content. © 1999 Elsevier Science B.V. All rights
reserved.
Keywords: Hydroxypropylcellulose; Hydroxypropylmethylcellulose; Substitution; Gas – liquid chromatography;
13
C-NMR spec-
troscopy; Raman spectroscopy
1. Introduction
Cellulose ethers (CEs) are a class of semisyn-
thetic polymers obtained by chemical reaction of
the hydroxyl groups at positions 2, 3 and/or 6 of
the anhydroglucose residues of cellulose. If only a
single kind of substituent group is present, they
are thus random copolymers of eight possible
glucopyranoses: the unsubstituted species, the
three possible monosubstituted species, the three
possible disubstituted species and the trisubsti-
tuted species. Their many industrial applications
* Corresponding author. Tel.: +34-981-594627; fax: +34-
981-547148.
E-mail address: ffancon@usc.es. (A. Concheiro)
0731-7085/99/$ - see front matter © 1999 Elsevier Science B.V. All rights reserved.
PII:S0731-7085(99)00066-7