High performance liquid chromatography analysis method for trace impurity content in organic amine catalyst
By derivatizing urea into DBU under acidic conditions, and combining it with a C18 reversed-phase column and gradient elution technology, the problem of urea detection in organic amine catalysts was solved, and efficient and accurate trace impurity analysis was achieved.
Patent Information
- Application Number
- CN202511973694.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-25
- Publication Date
- 2026-02-06
AI Technical Summary
Existing technologies struggle to quickly and accurately detect trace impurities in organic amine catalysts, especially urea, primarily because urea lacks ultraviolet absorption or fluorescence properties, resulting in insufficient detection sensitivity and poor separation performance.
Urea was converted into dibenzyl urea (DBU) with ultraviolet absorption by benzaldehyde derivatization under acidic conditions. The DBU was then detected by an ultraviolet detector using a C18 reversed-phase column and gradient elution technique.
It achieves highly sensitive detection of urea in organic amine catalysts, with good separation effect, simple operation, and strong reproducibility, and is suitable for qualitative and quantitative analysis of various trace impurities.
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Figure CN121476488A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the field of organic catalyst content analysis, in particular to a high-performance liquid chromatography analysis method for trace impurity content in an organic amine catalyst. BACKGROUND
[0002] Organic amine catalysts have important applications in the field of polyurethane and the like, and their substances include various compounds such as ethanolamine, diethanolamine, triethanolamine and related industrial mixtures. However, the trace impurities remaining in the synthesis process can seriously affect the performance of the catalyst and the quality of the final product. Therefore, accurate determination of the urea content in the system has important practical application needs. However, the complex matrix composition of organic amine substances poses a certain challenge to urea detection. Mainly because urea itself does not have strong ultraviolet absorption or fluorescence characteristics, it cannot be directly detected by conventional high-performance liquid chromatography (HPLC) ultraviolet / visible light detectors and other commonly used detection equipment. Currently, existing detection methods have problems such as insufficient sensitivity, poor separation effect, and complex operation when detecting trace impurities. Therefore, it is of great practical significance to develop a rapid, accurate, and highly selective analysis method. SUMMARY
[0003] The purpose of the present application is to provide a high-performance and accurate HPLC analysis method for trace impurity content in an organic amine catalyst.
[0004] The technical solution adopted by the present application is a high-performance liquid chromatography analysis method for trace impurity content in an organic amine catalyst, characterized by the following steps: Step S1: Pretreatment of organic amine catalyst sample; Accurately weigh the organic amine catalyst sample, dissolve and dilute the sample to constant volume, add benzaldehyde derivatization reagent and strong acid as catalyst to the diluted sample, and perform derivatization reaction at a set temperature, then cool the sample to room temperature and dilute to constant volume after derivatization reaction; Step S2: Preparation of urea standard solution; Weigh pure urea, dissolve and dilute to constant volume using the same solvent as in step S1, and prepare at least two groups of urea standard solutions by stepwise dilution. Derivatize the standard solutions under the same derivatization conditions as in step S1 to obtain the derivatized standard solutions; Step S3: High-performance liquid chromatography (HPLC) analysis; Perform HPLC analysis on the derivatized organic amine catalyst sample solution of step S1 and the derivatized urea standard solution of step S2 in sequence, with the following analysis conditions: use a C18 reversed-phase chromatographic column for separation, use methanol-water as the mobile phase for gradient elution, and detect at a wavelength of 254 nm; Step S4: Quantitative analysis by external standard method; Based on the HPLC analysis results of the urea standard solution, a standard curve of peak area Y versus urea concentration X is established, and the urea content in the organic amine catalyst sample is calculated according to the standard curve to complete the analysis.
[0005] Preferably, in step S1, the reagent used for dissolving the sample needs to be compatible with the derivatization reagent.
[0006] Preferably, the reaction conditions of the derivatization reaction are as follows: the mixture of the organic amine catalyst sample, the benzaldehyde derivatization reagent, and the strong acid catalyst is placed in a 60-70℃ constant temperature water bath or oven, and the constant temperature reaction is carried out for 15-30 minutes.
[0007] Preferably, in the sample pretreatment step of step S1, after dissolving and diluting, the sample also needs to be filtered, and a 0.22 μm filter membrane is used for filtering.
[0008] Preferably, in step S2, the concentration range of the urea standard solution is 0.5-50 mg / L, which completely covers the expected concentration range of urea in the sample.
[0009] Preferably, the gradient elution program of step S3 is as follows: the initial methanol: water = 50:50, adjusted to 20:80 at 10 min, 0:100 at 25 min, and returned to 50:50 at 30 min.
[0010] Preferably, the HPLC analysis conditions in step S3 also include: the eluent flow rate is 1.0 mL / min, the C18 reverse phase chromatographic column temperature is 30-40℃, and the sample injection amount is 10-20 μL.
[0011] Preferably, the mobile phase for elution in step S3 can also be acetonitrile-water, and the volume ratio is the same as that of methanol-water.
[0012] Preferably, in step S4, the urea content in the sample is calculated according to the standard curve, and the formula is as follows: urea content ; wherein: C is the urea concentration g / mL measured by HPLC, is the constant volume mL after derivatization, D is the dilution multiple, m is the sample mass g, is the sample volume mL used for derivatization, is the initial sample volume mL.
[0013] The application discloses a high-performance liquid chromatography analysis method for trace impurity content in an organic amine catalyst, wherein the trace impurity is mainly urea; the method successfully converts the urea without ultraviolet absorption into dibenzylidene urea (DBU) with strong ultraviolet absorption through a derivatization reaction of urea and benzaldehyde under an acidic condition, effectively fills the technical blank of direct detection of urea, and realizes accurate detection by adapting a conventional ultraviolet / visible light detector. BRIEF DESCRIPTION OF DRAWINGS
[0014] Figure 1 A blank control liquid chromatogram of a derivatization reagent; Figure 2 A liquid chromatogram of a standard urea after derivatization. DETAILED DESCRIPTION
[0015] The application is further illustrated below by combining the drawings Figure 1 and Figure 2 and specific examples, but the examples do not limit the application in any form.
[0016] The application is: a high-performance liquid chromatography analysis method for trace impurity content in an organic amine catalyst, characterized by comprising the following steps. Step S1: pretreatment of an organic amine catalyst sample; An organic amine catalyst sample is accurately weighed, diluted and dissolved, benzaldehyde derivatization reagent and strong acid as a catalyst are added to the diluted sample, a derivatization reaction is carried out at a set temperature under constant temperature, the sample after the derivatization reaction is cooled to room temperature and diluted and fixed. Step S2: preparation of a urea standard solution; Pure urea is weighed and prepared into at least two groups of urea standard solutions, the standard solutions are subjected to derivatization treatment under the same derivatization conditions of step S1, and the derivatized standard solutions are obtained; Step S3: HPLC analysis; The organic amine catalyst sample solution after derivatization of step S1 and the urea standard solution after derivatization of step S2 are sequentially subjected to HPLC analysis, and the analysis conditions are as follows: a C18 reversed-phase chromatographic column is used for separation, methanol-water is used as a mobile phase for gradient elution, and detection is carried out under a wavelength of 254 nm; Step S4: quantitative analysis by an external standard method; The HPLC analysis result of the urea standard solution is used as a basis to establish a standard curve of peak area Y versus urea concentration X, the urea content in the organic amine catalyst sample is calculated according to the standard curve, and the analysis is completed.
[0017] Preferably, in step S1, the reagent used to dissolve the sample needs to be compatible with the derivatization reagent.
[0018] Preferably, the reaction conditions for the derivatization reaction are as follows: the organic amine catalyst sample, the benzaldehyde derivatization reagent and the strong acid catalyst mixture are placed in a constant temperature water bath or oven at 60-70℃ and reacted at a constant temperature for 15-30 minutes.
[0019] Preferably, in the sample pretreatment step S1, after dissolution and dilution, the sample also needs to be filtered using a 0.22 μm filter membrane.
[0020] Preferably, in step S2, the concentration range of the urea standard solution is 0.5–50 mg / L, which completely covers the expected concentration range of urea in the sample.
[0021] Preferably, the gradient elution program in step S3 is as follows: the initial methanol:water ratio is 50:50 by volume, then adjusted to 20:80 at 10 min, adjusted to 0:100 at 25 min, and restored to 50:50 at 30 min.
[0022] Preferably, the HPLC analysis conditions in step S3 further include: an eluent flow rate of 1.0 mL / min, a C18 reversed-phase column temperature of 30-40℃, and an injection volume of 10-20 μL.
[0023] Preferably, the mobile phase used for elution in step S3 can also be acetonitrile-water, with the same volume ratio as methanol-water.
[0024] Preferably, in step S4, the urea content in the sample is calculated based on the standard curve, using the following formula: Urea content ; Where: C is the urea concentration (g / mL) measured by HPLC. The volume after derivatization is mL, D is the dilution factor, and m is the sample mass in g. The sample volume used for derivatization is mL. The initial volume of the sample is mL. Example
[0025] Taking the determination of residual urea content in 3-dimethylaminopropylurea as an example, the specific implementation method of the present invention is described as follows: 1. Sample pretreatment; Accurately weigh 0.1g of sample, dissolve it in methanol and dilute to 10mL.
[0026] To carry out the derivatization reaction, take 5 mL of sample solution, add 1 mL of 5% benzaldehyde methanol solution and 0.5 mL of 2M HCl (or 1-2 drops of concentrated H2SO4), react at 60℃ for 30 minutes, cool, and then dilute to 10 mL with methanol and filter.
[0027] 2. Prepare standard solutions by taking 1g and 5g of urea and making up to 100ml respectively, and then performing derivatization reaction treatment using the same sample pretreatment method.
[0028] 2. Perform HPLC analysis; (1) HPLC analysis conditions: Chromatographic column: C18 column (250 mm × 4.6 mm, 5 μm); mobile phase: gradient elution of methanol / ultrapure water (or acetonitrile / ultrapure water); flow rate: 0.6 mL / min; detection wavelength: 254 nm; injection volume: 20 μL; column temperature: 35 ℃.
[0029] (2) Gradient elution conditions: ; 3. Quantitative calculation: The urea content in the sample is calculated based on the standard curve using the following formula: Urea content ; Where: C is the urea concentration (g / mL) measured by HPLC. The volume after derivatization is mL, D is the dilution factor, and m is the sample mass in g. The sample volume used for derivatization is mL. The initial volume of the sample is mL.
[0030] Data Examples and Analysis: (1) Establishment of standard curve and linearity verification To verify the accuracy and reliability of the analytical method, standard solutions of organic amine catalysts with concentrations ranging from 0.5 to 50 mg / L were prepared. Analysis was performed under optimized chromatographic conditions, and a linear regression was conducted on peak area (Y) against concentration (X) to obtain the standard curve equation: y = 12546.8x + 18.3 R²=0.9998 The results indicate that, within the range of concentrations examined, the target analyte response exhibits a good linear relationship with concentration, with a linear correlation coefficient greater than 0.999, meeting the requirements for quantitative analysis.
[0031] (2) Sample determination and method validation The 3-dimethylaminopropylurea sample was pretreated and analyzed. The peak area of the impurity urea derivative was recorded, and its concentration was calculated based on the standard curve. Using batch 251,130 of our company's products as the test object, the residual urea content was found to be 0.024% (w / w).
[0032] To further evaluate the repeatability and precision of the method, six parallel experiments were conducted, and the results showed that: The relative standard deviation (RSD) is 2.35%. Average recovery rate = 98.7%.
[0033] Among them, by Figure 2 The liquid chromatogram of the standard urea derivatization showed that the peak at 9.294 min was the peak of the urea derivatization product.
[0034] The above data show that this method has good reproducibility and accuracy, and can meet the quantitative analysis requirements of trace impurities in organic amine catalysts.
[0035] Trace impurities in organic amine catalysts are mainly urea. Since urea itself has no UV absorption characteristics, direct detection is difficult; therefore, a derivatization method is used to address this issue. This invention involves the derivatization reaction of urea with benzaldehyde under acidic conditions, converting the non-UV-absorbing urea into DBU, which has strong UV absorption. Subsequently, using a reversed-phase C18 column combined with an optimizable methanol / water or acetonitrile / water mobile phase system, good baseline separation of DBU from unreacted organic amines, excess benzaldehyde, byproducts, and other components in the sample matrix can be achieved, significantly reducing matrix interference. By processing standards and samples under the same matrix and derivatization conditions, matrix effects can be effectively compensated, and quantification using external standard methods ensures stable and reliable detection results. This method has wide applicability; by adjusting the dilution factor, derivatization parameters (such as temperature, time, reagent concentration, etc.), and chromatographic conditions, it can be adapted to the detection of organic amine samples in different states (liquid and solid, after appropriate dissolution treatment) and with different urea contents, showing broad application prospects.
[0036] Furthermore, the specific embodiments used in this invention have been used to illustrate the content of this invention, but are not limited to these embodiments. Any obvious modifications made by those skilled in the art based on the teachings of this invention are within the scope of protection of this invention.
Claims
1. A high-performance liquid chromatography method for the analysis of trace impurities in organic amine catalysts, characterized in that, Includes the following steps: Step S1: Pretreatment of organic amine catalyst samples; Accurately weigh the organic amine catalyst sample, dissolve and dilute the sample to a certain volume, add benzaldehyde derivatization reagent and strong acid as catalyst to the diluted sample, carry out the derivatization reaction at a set temperature, cool the sample that has completed the derivatization reaction to room temperature and dilute to a certain volume. Step S2: Preparation of urea standard solution; Weigh out pure urea and prepare at least two sets of urea standard solutions. Derivatize the standard solutions under the same derivatization conditions as in step S1 to obtain the derivatized standard solutions. Step S3: High-performance liquid chromatography (HPLC) analysis; The organic amine catalyst sample solution derivatized in step S1 and the urea standard solution derivatized in step S2 were sequentially analyzed by HPLC. The analytical conditions were as follows: separation was performed using a C18 reversed-phase column, gradient elution was performed using methanol-water as the mobile phase, and detection was performed at a wavelength of 254 nm. Step S4: Perform quantitative analysis using the external standard method; Based on the HPLC analysis results of urea standard solution, a standard curve of peak area Y versus urea concentration X was established. The urea content in the organic amine catalyst sample was calculated based on the standard curve to complete the analysis.
2. The high-performance liquid chromatography method for analyzing trace impurities in organic amine catalysts according to claim 1, characterized in that: In step S1, the reagent used to dissolve the sample needs to be compatible with the derivatization reagent.
3. The high-performance liquid chromatography method for analyzing trace impurities in organic amine catalysts according to claim 1, characterized in that, The reaction conditions for the derivatization reaction are as follows: place the organic amine catalyst sample, benzaldehyde derivatization reagent and strong acid catalyst mixture in a constant temperature water bath or oven at 60-70℃ and react at a constant temperature for 15-30 minutes.
4. The high-performance liquid chromatography method for analyzing trace impurities in organic amine catalysts according to claim 1, characterized in that: In the sample pretreatment step S1, after dissolution and dilution, the sample also needs to be filtered using a 0.22 μm filter membrane.
5. The high-performance liquid chromatography method for analyzing trace impurities in organic amine catalysts according to claim 1, characterized in that: In step S2, the concentration range of the urea standard solution is 0.5–50 mg / L, which completely covers the expected concentration range of urea in the sample.
6. The high-performance liquid chromatography method for analyzing trace impurities in organic amine catalysts according to claim 1, characterized in that, The gradient elution program for step S3 is as follows: the initial methanol:water ratio is 50:50 by volume, then adjusted to 20:80 at 10 min, 0:100 at 25 min, and restored to 50:50 at 30 min.
7. The high-performance liquid chromatography method for analyzing trace impurities in organic amine catalysts according to claim 1, characterized in that, The HPLC analysis conditions in step S3 also include: an eluent flow rate of 1.0 mL / min, a C18 reversed-phase column temperature of 30-40℃, and an injection volume of 10-20 μL.
8. The high-performance liquid chromatography method for analyzing trace impurities in organic amine catalysts according to claim 6, characterized in that, The mobile phase used for elution in step S3 can also be acetonitrile-water, with the same volume ratio as methanol-water.
9. The high-performance liquid chromatography method for analyzing trace impurities in organic amine catalysts according to claim 1, characterized in that, Step S4: Calculate the urea content in the sample based on the standard curve, using the following formula: Urea content ; Where: C is the urea concentration (g / mL) measured by HPLC. The volume after derivatization is mL, D is the dilution factor, and m is the sample mass in g. The sample volume used for derivatization is mL. The initial volume of the sample is mL.