Hydroxyethylmethyl celluloses (HEMC, DS(Me) 1.46-1.66, DS(HE) = 0.14-0.17) have been analyzed with respect to their methyl and hydroxyethyl pattern in the glucosyl units and along the polymer chain. Methyl groups were located by GLC/MS after direct hydrolysis, reduction, and acetylation, and the distribution of hydroxyethyl residues in the glucosyl units could be determined with enhanced sensitivity after permethylation to unify a certain HE pattern occurring in combination with various methyl patterns in a single peak. To get insight into the distribution of Me and HE along the cellulose chain, a method was developed which overcomes the strong discrimination of relative ion intensities caused by hydroxyalkyl groups and enables quantitative determination of the oligomer composition after random degradation for the first time. This comprises perdeuteriomethylation; partial acid hydrolysis; reductive amination with propylamine; and, finally, permethylation to yield completely O- and N-alkylated, permanently charged oligosaccharides. Although the methyl pattern can be determined by electrospray ionization ion-trap mass spectrometry (ESI-IT-MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), as well, only MALDI-TOF-MS produced representative data for a quantitative evaluation of the HE pattern. Distribution of HE groups matches with a random distribution calculated from the monomer composition, whereas the methyl pattern was heterogeneous to a different extent.

The investigation of the substituent pattern of cellulose and starch ethers and esters on various structural levels as in the glucosyl unit, along the polymer chain, and over the polymer molecules, still is a very challenging task.By means of mass spectrometric methods as ESI‐MS or MALDI‐TOF‐MS the composition of oligosaccharide mixtures which represent the substituent distribution in the original polymer can principally be determined. However, to obtain reliable quantitative data mass spectra must be recorded under appropriate instrumental conditions and after special sample preparation While O‐methyl/O‐methyl‐d3‐oligosaccharides give representative data with the mentioned MS techniques and FAB‐MS as well, hydroxyalkyl ethers require labelling with a quaternary ammonium tag and MALDI‐TOF‐MS to prevent discrimination of lower substituted oligosaccharides. In this way, information on the neighbourhood of glucosyl units in the polymer chain is available which – together with the monomer composition – is a valuable parameter to describe a random or a heterogeneous pattern with regions of local higher densities of substituents compared to the random model, a regular distribution, or a block‐like substituent pattern, i.e. a more clustered localisation of substiuents in the polymer chain. In addition, tandem‐mass spectrometry (ESI‐MSn) allows to gain further insight in the composition of isomeric oligosaccharide derivatives of the same m/z ratio and to calculate the complete monomer composition of methyl celluloses.