Measurement of Diketene Using In Situ Derivatization-Headspace-Gas Chromatography

IF 1.2 4区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Chromatographia Pub Date : 2025-03-05 DOI:10.1007/s10337-025-04398-4

Noémi Göröcs, Balázs Volk

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Abstract

During the registration procedure of a drug substance, the actual and potential impurities must be summarized in a legal documentation. Diketene is a reactive chemical compound which is used for the introduction of an acetoacetyl structural unit into organic compounds. Since this material commonly used as a reagent in the pharmaceutical industry, it is a potential impurity of certain drug substances. The aim of this work was to develop and validate a suitable method for the analysis of diketene by means of decomposition headspace gas chromatography. The product of the derivatization reaction is acetone, which can be easily measured by gas chromatography. Various parameters have been integrated into the elaborated limit test validation, such as specificity, detection limit (LD), quantification limit (LQ), system precision, recovery at limit level, robustness and solution stability. The limits of detection and quantification are 60 and 200 ppm, respectively. Using the above-mentioned new analytical method, the concentration of diketene can be determined accurately. These precise measurements are necessary for the appropriate characterization of the drug substance, which is a prerequisite step of a marketing authorization for the finished product.

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原位衍生-顶空-气相色谱法测定双乙烯烯

在原料药的注册过程中，必须在法律文件中总结实际和潜在的杂质。双烯酮是一种活性化合物，用于在有机化合物中引入乙酰乙酰基结构单元。由于该物质通常在制药工业中用作试剂，因此它是某些原料药的潜在杂质。本工作的目的是建立和验证一种适用于分解顶空气相色谱法分析双烯酮的方法。衍生化反应的产物为丙酮，可以用气相色谱法测定。将特异性、检出限（LD）、定量限（LQ）、系统精密度、极限回收率、鲁棒性和溶液稳定性等参数集成到详细的限度检验验证中。检测限为60 ppm，定量限为200 ppm。采用上述新的分析方法，可以准确地测定双烯酮的浓度。这些精确的测量对于原料药的适当表征是必要的，这是成品上市许可的先决条件。

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来源期刊

Chromatographia 化学-分析化学

CiteScore

3.40

自引率

5.90%

发文量

103

审稿时长

2.2 months

期刊介绍： Separation sciences, in all their various forms such as chromatography, field-flow fractionation, and electrophoresis, provide some of the most powerful techniques in analytical chemistry and are applied within a number of important application areas, including archaeology, biotechnology, clinical, environmental, food, medical, petroleum, pharmaceutical, polymer and biopolymer research. Beyond serving analytical purposes, separation techniques are also used for preparative and process-scale applications. The scope and power of separation sciences is significantly extended by combination with spectroscopic detection methods (e.g., laser-based approaches, nuclear-magnetic resonance, Raman, chemiluminescence) and particularly, mass spectrometry, to create hyphenated techniques. In addition to exciting new developments in chromatography, such as ultra high-pressure systems, multidimensional separations, and high-temperature approaches, there have also been great advances in hybrid methods combining chromatography and electro-based separations, especially on the micro- and nanoscale. Integrated biological procedures (e.g., enzymatic, immunological, receptor-based assays) can also be part of the overall analytical process.