Measurement of solution properties and molecular weight of hydroxyethyl starches using multi-angle laser light...

The solution properties of hydroxyethyl starch (HES) vary significantly owing to different measurement parameters adopted and sample structures. Here, a round-robin study was conducted to compare inter-laboratory measurements of solution properties, weight-average molecular weight (M_w), and molecular weight distribution of four HES candidates covering the low- and medium-molecular-weight range, and 50 commercially available HES 130/0.4 drug samples. Analysis was performed using size exclusion chromatography (SEC) combined with multi-angle laser light scattering (MALLS) and differential refractive index (dRI) detectors. The results indicate that HES molecules in the M_w range of 17,000-130,000, with varying degrees of substitution (between 0.4 and 0.8), yielded a refractive index increment (dn/dc) value of 0.145 ± 0.003 mL/g (solvent: acetic acid-sodium acetate buffer; wavelength: 658 nm) and that the second virial coefficient (A₂) is correlated with M_w. The SEC-MALLS-dRI method for M_w determination of HES demonstrated good inter-laboratory reproducibility; however, the study findings suggest that column specifications should be added for HES quality standards. Comparing M_w results obtained using common and experimentally corrected dn/dc and A₂ values revealed an influence of dn/dc and A₂ on M_w, indicating that the M_w acceptance criteria of HES quality standards should be adjusted.