Quantification of aldehyde impurities in poloxamer by 1H NMR spectrometry

This work presents a fast and simple quantitative method for impurity determination of acetaldehyde and propionaldehyde in poloxamer 188 by proton nuclear magnetic resonance spectroscopy (H-1 NMR). The sample is dissolved in D2O with DCl and analyzed with a 600 MHz NMR spectrometer. Data processing, including filtering by convolution of spectra with a triangular function and integration, is performed in MATLAB. The repeated studies of one sample, including automatic gradient shimming and data processing, revealed a relative standard deviation (R.S.D.) of 2.8%. For the reproducibility, also including sample preparation, the R.S.D. was less than 10%. The predictability of a linear calibration model was estimated by the root mean square error of prediction from leave-one-out cross-validation (RMSECV). Using 64 scans, RMSECV was found to be 7.2 and 5.5 mu g g(-1) for acetaldehyde and propionaldehyde respectively for a 4.3-min acquisition time. The limits of detection, defined as three times the noise, reached 19 and 15 mu g g(-1) respectively under the same experimental conditions. These limits are sufficient to quantify 80 and 100 mu g g(-1) of the impurities, which has been found to be the maximum allowed content in the poloxamer for some medical applications. Thus the method has the potential to replace the current liquid chromatography (LC) method for impurity determination of acetaldehyde and propionaldehyde in poloxamer, which is time-consuming and includes a work-up procedure involving many steps. (c) 2005 Elsevier B.V. All rights reserved.