Quantitative determination and validation of octreotide acetate using ¹H‐NMR spectroscopy with internal standard method

Abstract

Quantitative nuclear magnetic resonance (qNMR) is a well-established technique in quantitative analysis. We presented a validated H-qNMR method for assay of octreotide acetate, a kind of cyclic octopeptide. Deuterium oxide was used to remove the undesired exchangeable peaks, which was referred to as proton exchange, in order to make the quantitative signals isolated in the crowded spectrum of the peptide and ensure precise quantitative analysis. Gemcitabine hydrochloride was chosen as the suitable internal standard. Experimental conditions, including relaxation delay time, the numbers of scans, and pulse angle, were optimized first. Then method validation was carried out in terms of selectivity, stability, linearity, precision, and robustness. The assay result was compared with that by means of high performance liquid chromatography, which is provided by Chinese Pharmacopoeia. The statistical F test, Student's t test, and nonparametric test at 95% confidence level indicate that there was no significant difference between these two methods. qNMR is a simple and accurate quantitative tool with no need for specific corresponding reference standards. It has the potential of the quantitative analysis of other peptide drugs and standardization of the corresponding reference standards.

Quantitative Determination of Acrolein in Cider by 1H NMR Spectrometry

“…In addition, it is soluble in water and produces a strong and clear singlet signal, which never overlaps with any other signal of the ciders. The use of internal standards in quantitative 1 H NMR is a common procedure used in many determination methods [26][27][28][29][30]. TSP ((CH 3 ) 3 -Si-CD 2 -CD 2 -COONa) was soluble in water and had a simple 1 H NMR spectrum with a single nine proton singlet, corresponding the three methyl groups -CH 3 .…”

Simultaneous Determination of the Saponification Value, Acid Value, Ester Value, and Iodine Value in Commercially Available Red Fruit Oil (Pandanus conoideus, Lam.) Using 1H qNMR Spectroscopy

“…The demand for speed and effectiveness of analytical methods, thereby resulting in high accuracy and precision, has increasingly become priority in recent years. One of the most promising methods for overcoming these challenges is quantitative nuclear magnetic resonance (qNMR) (Yu et al 2018). The guidance on the use of qNMR and its application for quantitative purposes was reviewed by Holzgrabe (2010) and Beyer et al (2010a) by depicting the quantitative analysis of oversulfated chondroitin sulfate and dermatan sulfate in heparin glycosaminoglycans.…”

Determination of isotope abundance for deuterium‐labeled compounds by quantitative 1H NMR + 2H NMR

“…The method shows universal sensitivity to all compounds that have C‐H structures, which means that it can analyze almost all kinds of organic compounds. Based on its favorable traits, such as simple and controllable pretreatment steps, rapid processing of analyses and high degree of accuracy, qNMR has been applied for the quantification of many compounds 25–28 . However, it has not been widely used for the quantification of deuterated reagents other than D 2 O. Goldblatt et al 29 first applied NMR to determine the isotopic abundance of D 2 O. NMR has shown results comparable with those of MS and density methods.…”

“…Based on its favorable traits, such as simple and controllable pretreatment steps, rapid processing of analyses and high degree of accuracy, qNMR has been applied for the quantification of many compounds. [25][26][27][28] However, it has not been widely used Long Xie and Yameng Zhao contribute equally to this work.…”