Objective: To establish an 1H quantitative nuclear magnetic resonance (1H qNMR) method for determination of the average molecular weight of poloxamer. Methods: The terminal hydroxyl groups of poloxamer were reacted with 2-fluorophenyl isocyanate in the presence of dibutyltin dilaurate as a catalyst. This reaction enabled separation of the signals of the terminal methylene groups from other methylene groups in the 1H qNMR spectrum. Deuterated chloroform was used as the solvent. The 1H qNMR spectra were collected at a constant temperature of 298 K using a Bruker Avance NEO 600 MHz NMR spectrometer with a pulse sequence of zg 30, a relaxation delay of 10 s, and 16 scans. Results: The established method demonstrated good specificity and robustness. The sample solutions were stable within 48 h, with a precision RSD (n=6) of 0.54%. The average molecular weights of different poloxamer varieties determined by 1H qNMR were 7 725.9, 10 533.9, 3 248.8, 5 545.6, and 13 409.8, which were consistent with the results obtained by the end-group titration method described in the Chinese Pharmacopoeia(7 831.2, 10 635.6, 3 315.8, 5 639.0, and 13 497.1), indicating good accuracy of the 1H qNMR method. Conclusion: The established 1H qNMR method is suitable for determining the average molecular weight of poloxamer. This method is a relative quantification approach that does not require internal standards or reference substances. It features a simple preparation process, rapid detection, good repeatability, strong specificity, and high accuracy, making it a valuable supplementary method for determining the average molecular weight of poloxamer.
ZHENG Yan
,
CHU Shao-jie
,
XU Wen-yu
,
LI Na-qiu
,
WANG Hong-bo
,
JIA You-zhi
. Study on the 1H qNMR method of average molecular weight of poloxamer[J]. Chinese Journal of Pharmaceutical Analysis, 2025
, 45(4)
: 598
-604
.
DOI: 10.16155/j.0254-1793.2024-1163
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