A method for determining the content of ethyltriphenylphosphonium bromide

Abstract

The application relates to the technical field of analysis methods, and specifically discloses a method for determining the content of ethyltriphenylphosphonium bromide, which adopts a high-performance liquid chromatography method, uses a C18 stainless steel column as a chromatographic column, uses a mixed solution of acetonitrile and a 0.1% potassium dihydrogen phosphate aqueous solution as a mobile phase, has a flow rate of 1.0 mL / min, a column temperature of 40 DEG C, a detection wavelength of 230 nm, a sample injection volume of 1.0 mu L, carries out isocratic elution, and calculates the content of ethyltriphenylphosphonium bromide and the residual amount of triphenylphosphine impurities by using an area normalization method. According to the molecular characteristics of ethyltriphenylphosphonium bromide, a specific small-molecule quaternary phosphonium salt, the chromatographic conditions such as the mobile phase system, the proportion and the detection wavelength are optimized, the content determination of the main component and the residual detection of triphenylphosphine impurities can be simultaneously completed under the same chromatographic conditions, the method is simple in operation, good in separation degree, high in sensitivity, good in reproducibility, and suitable for industrial quality control of ethyltriphenylphosphonium bromide.

Description

Technical Field

[0001] This invention relates to the field of analytical methods, specifically to a method for determining the content of ethyltriphenylphosphine bromide. Background Technology

[0002] Ethyltriphenylphosphonium bromide (CAS No. 1530-32-1, molecular formula C) 20 H 20 BrP (molecular weight 371.25), also known as ethyltriphenylphosphine bromide, is an important quaternary phosphonium salt compound. It appears as a white to grayish-white crystalline powder with a melting point of 203–205 °C. As a classic Wittig reagent precursor, ethyltriphenylphosphine bromide has wide applications in organic synthesis. It can react with carbonyl compounds such as aldehydes and ketones via the Wittig reaction to prepare olefins, making it a key raw material in the synthesis of fine chemicals and pharmaceutical intermediates. Furthermore, ethyltriphenylphosphine bromide can also be used as a catalyst and a phase transfer catalyst. With its expanding applications in various fields, market demand is increasing year by year, placing higher demands on product quality control.

[0003] Ethyltriphenylphosphine bromide is typically prepared by a nucleophilic substitution reaction between triphenylphosphine and bromoethane. In this synthesis, the lone pair of electrons from the phosphorus atom in the triphenylphosphine molecule attacks the carbon atom of bromoethane, generating ethyltriphenylphosphine bromide. Since the conversion rate is rarely 100%, unreacted triphenylphosphine residues inevitably remain in the product. These residual triphenylphosphine impurities not only affect the purity of the ethyltriphenylphosphine bromide product but also interfere with the stereoselectivity and yield of the downstream Wittig reaction. Therefore, accurate detection of residual triphenylphosphine impurities is a crucial aspect of quality control. Furthermore, the content of the main component of ethyltriphenylphosphine bromide directly affects the stoichiometric accuracy of its use as a synthetic reagent, necessitating the establishment of accurate and reliable quantitative analytical methods.

[0004] High-performance liquid chromatography (HPLC) has become the mainstream method for the determination of organophosphorus compounds due to its advantages such as high separation efficiency, high sensitivity, and fast analysis speed. Existing technologies include HPLC analysis methods for triphenylphosphine bromide derivatives. Patent CN113092597B discloses an analytical method for related substances of pitavastatin calcium intermediate [[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolinyl]methyl]triphenylphosphine bromide (CAS154057-58-6, molecular weight 618.5). The method uses an Agilent ZORBAX SB-C18 column (150×4.6 mm, 5 μm), with a mobile phase of 0.02 mol / L ammonium acetate buffer (adjusted to pH 7.2 with triethylamine)-acetonitrile (25:75), a detection wavelength of 245 nm, a column temperature of 40 °C, a flow rate of 1.0 mL / min, an injection volume of 10 μL, isocratic elution, and the content of each impurity is calculated using the area normalization method. This method can effectively separate the triphenylphosphine bromide intermediate and its six related substances, with a resolution greater than 1.5 for all. However, 1. The compounds detected by this method have significantly different structures and cannot be directly applied: The analyte in this method has a molecular weight of 618.5 and contains large substituents such as a quinoline ring, fluorophenyl, and cyclopropyl groups. Its molecular structure, polarity characteristics, and chromatographic retention behavior differ significantly from ethyltriphenylphosphine bromide (molecular weight 371.25, containing only ethyl substituents). Therefore, the chromatographic conditions of this method cannot be directly applied to the analysis of ethyltriphenylphosphine bromide. 2. The separation chemical mechanisms are different: This patent uses a neutral or weakly alkaline ammonium acetate buffer (pH 7.0-8.0) as the mobile phase, which easily leads to severe peak tailing problems. Furthermore, patent CN118010865A discloses an HPLC method for detecting homologues of 4-carboxybutyltriphenylphosphine bromide (CAS17814-85-6, molecular weight 443.31). This method uses an octadecylsilane-bonded silica (C18) column as the packing material and a mobile phase of phosphoric acid aqueous solution (0.01%-0.1% by volume)-acetonitrile, wherein the volume ratio of phosphoric acid aqueous solution to acetonitrile is 80:20-70:30, i.e., elution with a high aqueous phase ratio. This method can achieve a resolution greater than 1.5 for 4-carboxybutyltriphenylphosphine bromide and its homologues, with a tailing factor not exceeding 1.5. However, the 4-carboxybutyltriphenylphosphine bromide molecule contains a free carboxyl group (-COOH), which is highly polar and requires a high proportion of aqueous phase to increase its retention on the reversed-phase column. Ethyltriphenylphosphine bromide, on the other hand, is a purely hydrocarbon-substituted quaternary phosphonium salt with strong hydrophobicity. Using the same high proportion of aqueous phase in the mobile phase would result in excessively long retention times and peak broadening, which is detrimental to efficient analysis. Furthermore, this method uses an aqueous phosphoric acid solution instead of a phosphate buffer solution, lacking pH buffering capacity, which may make it difficult to obtain ideal peak shapes for quaternary phosphonium salts existing in cationic form in solution. This method also does not disclose key chromatographic parameters such as flow rate, column temperature, detection wavelength, injection volume, and quantification method.In addition, existing technologies also report a method for the quantitative analysis of industrial triphenylphosphine using an ODS (250×4.6mm, 10μm) stainless steel column, a methanol-water (4:1) mobile phase, a flow rate of 1.5mL / min, and a UV detection wavelength of 254nm, employing an external standard method. This method is suitable for the quantitative analysis of triphenylphosphine itself, but it uses a methanol-water system instead of an acetonitrile-phosphate system, and it does not cover the detection of ethyltriphenylphosphine bromide.

[0005] Therefore, there is still a need in this field to develop a high-performance liquid chromatography (HPLC) method specifically for the analysis of ethyltriphenylphosphine bromide. Summary of the Invention

[0006] This invention provides a method for determining the content of ethyltriphenylphosphine bromide. Addressing the lack of specific high-performance liquid chromatography (HPLC) methods for determining the content of ethyltriphenylphosphine bromide and detecting residual triphenylphosphine impurities in existing technologies, this invention provides a simple, accurate, and reliable HPLC method. It can simultaneously perform the quantitative determination of the main component content of ethyltriphenylphosphine bromide and the detection of residual triphenylphosphine impurities under the same chromatographic conditions. Furthermore, it maintains stable column operation, reduces peak distortion caused by solvent effects, and ensures peak symmetry and quantitative accuracy.

[0007] To address the above technical problems, this invention provides a method for determining the content of ethyltriphenylphosphine bromide, employing high-performance liquid chromatography (HPLC), comprising the following steps: S1. Sample solution preparation: Weigh the ethyltriphenylphosphine bromide sample, dissolve it in acetonitrile, sonicate, cool to room temperature, dilute with acetonitrile to volume, shake well, filter, and obtain the sample solution. S2. Chromatographic determination: The sample solution is injected into a high-performance liquid chromatograph equipped with an ultraviolet detector for detection, and the chromatogram is recorded; wherein, the chromatographic conditions for the high-performance liquid chromatography are: Column: C18 stainless steel column packed with octadecylsilane-bonded silica gel; Mobile phase: a mixed solution of acetonitrile and potassium dihydrogen phosphate aqueous solution; wherein the mass percentage concentration of the potassium dihydrogen phosphate aqueous solution is 0.1%; and the volume ratio of acetonitrile to potassium dihydrogen phosphate aqueous solution is 70:30~80:20. Flow rate: 1.0 mL / min; Column temperature: 40℃; Detection wavelength: 230nm; Injection volume: 1.0 μL; Elution method: isocratic elution; S3. Content Calculation: The content of ethyltriphenylphosphine bromide and the residual amount of triphenylphosphine impurities are calculated using the area normalization method.

[0008] Furthermore, the potassium dihydrogen phosphate aqueous solution is prepared by dissolving 1.0 g of potassium dihydrogen phosphate in 1000 mL of water and shaking well.

[0009] Furthermore, the chromatographic column has a size of 250 mm × 4.6 mm and a packing particle size of 5 μm.

[0010] Furthermore, the volume ratio of the acetonitrile and the potassium dihydrogen phosphate aqueous solution is 70:30.

[0011] Furthermore, the volume ratio of the acetonitrile and the potassium dihydrogen phosphate aqueous solution is 80:20.

[0012] Furthermore, in S2, the running time for the chromatographic determination is 30.0 min.

[0013] Furthermore, in S1, 0.1 g of the ethyltriphenylphosphine bromide sample is weighed and placed in a 25 mL volumetric flask and diluted to volume.

[0014] Furthermore, in S1, the duration of the ultrasonic oscillation is 5 minutes.

[0015] Furthermore, in S1, the filtration uses a filter membrane with a pore size of 0.45 μm.

[0016] Compared with existing technologies, this solution has the following advantages: 1. Molecular characteristics of mobile phase systems adapted to ethyltriphenylphosphine bromide This invention uses a 0.1% potassium dihydrogen phosphate aqueous solution as the aqueous component of the mobile phase. Potassium dihydrogen phosphate is an inorganic buffer salt that dissociates in solution to produce H2PO4. - Anion, quaternary phosphorus cation of ethyltriphenylphosphine bromide ([C2H5P) + (C6H5)3) exhibits ion-pair effect, effectively improving the peak shape of quaternary phosphonium salts on reversed-phase chromatography columns and reducing tailing. Furthermore, potassium dihydrogen phosphate solution (pH approximately 4.5-5.0) provides a stable, weakly acidic buffer environment, keeping the mobile phase pH within the column's tolerance range, which is beneficial for the long-term stable operation of the chromatography system. Compared to the ammonium acetate buffer system (pH 7.2) used in the existing technology CN113092597B, the potassium dihydrogen phosphate system has a lower pH, closer to the optimal pH range for C18 columns, and avoids interference from ammonium salts' ultraviolet absorption at low wavelengths. Compared to the phosphoric acid aqueous solution (non-buffered salt) used in the existing technology CN118010865A, potassium dihydrogen phosphate has a clear pH buffering capacity, resisting pH fluctuations introduced by the sample solution and ensuring the reproducibility of retention times.

[0017] 2. Matching the mobile phase ratio with the hydrophobicity of the analyte. This invention employs a high organic phase ratio of acetonitrile to 0.1% potassium dihydrogen phosphate aqueous solution at a volume ratio of 70:30 or 80:20, which matches the hydrophobic characteristics of ethyltriphenylphosphine bromide. Ethyltriphenylphosphine bromide is a pure hydrocarbon-substituted quaternary phosphonium salt with moderate logP and strong hydrophobicity. The high organic phase ratio effectively controls the retention time within a reasonable range, avoiding peak broadening and prolonged analysis time due to excessive retention. In contrast, existing technology CN118010865A uses a high aqueous phase ratio (70%~80% aqueous phase) for 4-carboxybutyltriphenylphosphine bromide containing free carboxyl groups. Directly applying this condition to ethyltriphenylphosphine bromide would result in excessively long retention times, making efficient analysis impossible.

[0018] 3. Optimized detection wavelength to improve sensitivity This invention uses 230nm as the detection wavelength. Compared with the 245nm in the prior art CN113092597B and the 254nm reported in the literature, 230nm is closer to the maximum absorption position of the B absorption band of the benzene ring of the triphenylphosphine skeleton in the ethyltriphenylphosphine molecule (around 230nm), which can obtain higher detection sensitivity and is beneficial for the accurate quantification of trace triphenylphosphine impurities.

[0019] 4. Small injection volume combined with acetonitrile solvent reduces solvent effect. This invention uses an injection volume of 1.0 μL and acetonitrile as the sample solvent. Because the mobile phase contains a high proportion of acetonitrile (70%~80%), the elution strength of the sample solution is close to that of the mobile phase when acetonitrile is used as the solvent. The small injection volume of 1.0 μL further reduces peak distortion caused by the solvent effect, ensuring the symmetry of the chromatographic peaks and the accuracy of quantification.

[0020] 5. The method has good reproducibility and is easy to operate. This invention employs isocratic elution, eliminating the need for gradient procedures and simplifying operation; an analysis can be completed within 30 minutes, resulting in high analytical efficiency; the area normalization method eliminates the need for reference standards, reducing analytical costs and making it suitable for routine testing in industrial product quality control. Detailed Implementation

[0021] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0022] The reagents and instruments used in the following examples are as follows: 1. Reagents: Water: Freshly distilled double-distilled water; Acetonitrile: chromatographic grade; Potassium dihydrogen phosphate: analytical grade; 0.1% potassium dihydrogen phosphate aqueous solution: Weigh 1.0g of potassium dihydrogen phosphate and dissolve it in 1000mL of water, then shake well; Ethyltriphenylphosphine bromide sample: prepared in-house, obtained by reacting triphenylphosphine with bromoethane; Triphenylphosphine reference standard: commercially available, purity ≥99.0%; Ethyltriphenylphosphine bromide reference standard: commercially available, purity ≥99.5%.

[0023] 2. Instruments: High-performance liquid chromatograph: equipped with a variable wavelength ultraviolet detector; Chromatographic column: 250mm × 4.6mm (id) stainless steel column, packed with C18 (octadecylsilane bonded silica gel) with a particle size of 5μm; Microsyringe: 10 μL; Electronic balance: Sensitivity 0.0001g; Volumetric flask: 25 mL; Ultrasonic cleaner; Filter: Membrane pore size 0.45μm; Chromatography workstation.

[0024] Example 1 Chromatographic conditions: Chromatographic column: C18 stainless steel column (250mm×4.6mm, 5μm); Mobile phase: Acetonitrile: 0.1% potassium dihydrogen phosphate aqueous solution = 70:30 (volume ratio); Flow rate: 1.0 mL / min; Column temperature: 40℃; Detection wavelength: 230nm; Injection volume: 1.0 μL; Runtime: 30.0 min; Elution method: isocratic elution.

[0025] Sample solution preparation: Weigh approximately 0.1 g (accurate to 0.0002 g) of ethyltriphenylphosphine bromide sample into a 25 mL volumetric flask, dissolve it in acetonitrile, sonicate for 5 min, remove the flask, cool to room temperature, dilute to the mark with acetonitrile, shake well, filter through a 0.45 μm filter membrane, and set aside for later use.

[0026] System suitability solution preparation: Weigh approximately 0.1 g of ethyltriphenylphosphine bromide sample and approximately 5 mg of triphenylphosphine reference standard into the same 25 mL volumetric flask, dissolve and dilute to the mark with acetonitrile, shake well, filter, and set aside.

[0027] Measurement steps: After the instrument baseline stabilizes, inject 1.0 μL of system suitability solution and record the chromatogram to confirm the resolution between the ethyltriphenylphosphine bromide peak and the triphenylphosphine peak. Then, inject several injections of sample solution consecutively, record the chromatograms, and calculate the ethyltriphenylphosphine bromide content and the residual amount of triphenylphosphine impurity using the area normalization method.

[0028] result: Under the above chromatographic conditions, the retention time of ethyltriphenylphosphine bromide was approximately 8.5 min, and the retention time of triphenylphosphine was approximately 5.2 min. The resolution between the two was 3.2 (greater than 1.5), and the theoretical plate number calculated based on the ethyltriphenylphosphine bromide peak was not less than 5000. The tailing factor of the ethyltriphenylphosphine bromide peak was 1.05.

[0029] The results of the determination of 6 consecutive sample solutions showed that the RSD of ethyltriphenylphosphine bromide content was 0.08% and the RSD of triphenylphosphine impurity residue was 1.2%, indicating good reproducibility of the method.

[0030] Area normalization calculation formula:

[0031]

[0032] in: w1: Mass percentage of ethyltriphenylphosphonium bromide, % w2: Percentage of triphenylphosphine impurity by mass, % A1: Peak area of ​​ethyltriphenylphosphonium bromide A2: Peak area of ​​triphenylphosphine impurity chromatographic parameters ΣA i The sum of the areas of all chromatographic peaks Example 2 Chromatographic conditions: Chromatographic column: C18 stainless steel column (250mm×4.6mm, 5μm); Mobile phase: Acetonitrile: 0.1% potassium dihydrogen phosphate aqueous solution = 80:20 (volume ratio); Flow rate: 1.0 mL / min; Column temperature: 40℃; Detection wavelength: 230nm; Injection volume: 1.0 μL; Runtime: 30.0 min; Elution method: isocratic elution.

[0033] Sample solution preparation: Same as in Example 1.

[0034] Measurement procedure: Same as in Example 1.

[0035] result: Under a mobile phase ratio of 80:20, the retention time of ethyltriphenylphosphine bromide was approximately 5.8 min, and the retention time of triphenylphosphine was approximately 3.5 min. The resolution between the two was 2.8 (greater than 1.5), and the theoretical plate number calculated based on the ethyltriphenylphosphine bromide peak was not less than 4000. The tailing factor of the ethyltriphenylphosphine bromide peak was 1.08.

[0036] The RSD of ethyltriphenylphosphine bromide content was 0.10% and the RSD of triphenylphosphine impurity residue was 1.5% after six consecutive injections.

[0037] Compared to Example 1, the 80:20 ratio results in a shorter retention time and faster analysis speed, but a slightly lower resolution, still meeting the requirements for quantitative analysis. Both ratios can be used for the determination of ethyltriphenylphosphine bromide content, and the choice can be made based on the impurity content level in the actual sample: when the impurity content is high and higher resolution is required, 70:30 is preferred; when rapid analysis is required, 80:20 can be selected.

[0038] Example 3 (Methodological Validation - Linearity and Range) Chromatographic conditions: Same as in Example 1.

[0039] Test method: Accurately weigh an appropriate amount of ethyltriphenylphosphine bromide reference standard and prepare a series of standard solutions with concentrations of 0.1, 0.5, 1.0, 2.0, 4.0, and 6.0 mg / mL using acetonitrile. Inject 1.0 μL of each solution and record the chromatograms. Perform linear regression on peak area (A) against concentration (C, mg / mL).

[0040] result: Ethyltriphenylphosphine bromide showed good linearity in the concentration range of 0.1–6.0 mg / mL, with a regression equation of A = 35.624C + 0.082 and a correlation coefficient r = 0.9996. This indicates that the method has a good linear response over a wide concentration range.

[0041] Example 4 (Method Validation - Limit of Detection and Limit of Quantification) Chromatographic conditions: Same as in Example 1.

[0042] Test method: Ethyltriphenylphosphine bromide and triphenylphosphine reference standards were progressively diluted and injected. The limit of detection (LOD) was determined with a signal-to-noise ratio (S / N) of 3, and the limit of quantitation (LOQ) was determined with a signal-to-noise ratio (S / N) of 10.

[0043] result:

[0044] The results show that the proposed method has high detection sensitivity at a detection wavelength of 230 nm, which can meet the quantitative detection requirements for trace amounts of triphenylphosphine impurities in ethyltriphenylphosphine bromide.

[0045] Example 5 (Method Validation - Accuracy Spike Recovery Test) Chromatographic conditions: Same as in Example 1.

[0046] Test method: Take a sample of ethyltriphenylphosphine bromide with a known content, add triphenylphosphine reference standard to make the spiking levels 0.1%, 0.5% and 1.0% (relative to the sample amount), prepare 3 portions for each level, determine the triphenylphosphine content according to the method of the present invention, and calculate the recovery rate.

[0047] result:

[0048] The recoveries of triphenylphosphine spiked to the sample ranged from 98.0% to 102.0%, with RSDs all less than 3%, indicating that the method was accurate.

[0049] Example 6 (Method Validation - Solution Stability) Chromatographic conditions: Same as in Example 1.

[0050] Test method: Take the same test solution and inject it at 0, 2, 4, 8, 12 and 24 h after preparation. Record the chromatogram and calculate the content of ethyl triphenylphosphine bromide and the residual amount of triphenylphosphine impurity at each time point.

[0051] result:

[0052] The RSD of ethyltriphenylphosphine bromide content in the test solution was 0.01% within 24 hours, and the residual amount of triphenylphosphine showed no obvious trend, indicating that the solution has good stability and meets the needs of routine analysis.

[0053] Example 7 (Measurement of actual samples) Chromatographic conditions: Same as in Example 1.

[0054] Test method: Take three batches of industrial samples of ethyltriphenylphosphine bromide and determine them according to the method of this invention, with each batch being determined in parallel three times.

[0055] result:

[0056] The test results of the three batches of samples all showed that this method can accurately determine the content of the main component of ethyltriphenylphosphine bromide and effectively monitor the residual level of triphenylphosphine impurities.

[0057] Comparative Example 1 Objective: To verify the technical effect of potassium dihydrogen phosphate aqueous phase relative to ammonium acetate aqueous phase.

[0058] Chromatographic conditions: Except that the mobile phase was changed from aqueous solution to 0.02 mol / L ammonium acetate buffer solution (adjusted to pH 7.2 with triethylamine), the other conditions were the same as in Example 1. The mobile phase was acetonitrile:0.02 mol / L ammonium acetate buffer solution = 70:30.

[0059] result:

[0060] Comparative Example 1 used an ammonium acetate system (referring to the aqueous phase type in CN113092597B). The tailing factor for the ethyltriphenylphosphine bromide peak was 1.32 (greater than 1.2), and the triphenylphosphine peak showed severe tailing, poor peak shape, and a resolution reduced to 2.1. In contrast, the potassium dihydrogen phosphate system of this invention had a tailing factor of 1.05, significantly improved peak symmetry, and a resolution increased to 3.2. This indicates that potassium dihydrogen phosphate has a significantly better ion-pairing effect on quaternary phosphonium cations than ammonium acetate, effectively improving the chromatographic peak shape.

[0061] Comparative Example 2 Objective: To verify the technical effect of a high organic phase ratio compared to a high water phase ratio.

[0062] Chromatographic conditions: Except for the mobile phase ratio being changed to 0.1% potassium dihydrogen phosphate aqueous solution: acetonitrile = 70:30 (high aqueous phase, referring to the ratio direction of CN118010865A), the other conditions are the same as in Example 1.

[0063] result:

[0064] Comparative Example 2, employing a high aqueous phase ratio (referencing the ratio direction in CN118010865A), extended the retention time of ethyltriphenylphosphine bromide to 42.3 min, with severe peak broadening (peak width 1.82 min). Within a 30-min run time, the main peak failed to emerge, rendering effective analysis impossible. In contrast, the high organic phase ratio of this invention controlled the retention time to 8.5 min, allowing for the completion of all analyses, including those involving triphenylphosphine impurities, within 30 min, significantly improving analytical efficiency. This demonstrates that for ethyltriphenylphosphine bromide, a highly hydrophobic small-molecule quaternary phosphonium salt, a high organic phase ratio is necessary to obtain reasonable retention behavior.

[0065] Comparative Example 3 Objective: To verify the technical effectiveness of the 230nm detection wavelength compared to 254nm and 245nm.

[0066] Chromatographic conditions: Except for the detection wavelengths being changed to 254nm and 245nm respectively, the other conditions are the same as in Example 1.

[0067] result:

[0068] At a detection wavelength of 230 nm, the response values ​​of ethyltriphenylphosphine bromide and triphenylphosphine were significantly higher than those at 245 nm and 254 nm. In particular, for trace triphenylphosphine impurities, the signal-to-noise ratio (S / N=42) at 230 nm was 1.5 times that at 245 nm (S / N=28) and 2.2 times that at 254 nm (S / N=19), respectively, indicating a significant improvement in detection sensitivity, which is more conducive to the accurate quantification of trace impurities.

[0069] The above descriptions are merely embodiments of the present invention, and common knowledge regarding specific structures and characteristics is not elaborated upon here. It should be noted that those skilled in the art can make various modifications and improvements without departing from the structure of the present invention, and these should also be considered within the scope of protection of the present invention. These modifications and improvements will not affect the effectiveness of the present invention or the practicality of the patent. The scope of protection claimed in this application should be determined by the content of its claims, and the specific embodiments described in the specification can be used to interpret the content of the claims.

Claims

1. A method for determining the content of ethyltriphenylphosphine bromide, characterized in that: The high-performance liquid chromatography method includes the following steps: S1. Sample solution preparation: Weigh the ethyltriphenylphosphine bromide sample, dissolve it in acetonitrile, sonicate, cool to room temperature, dilute with acetonitrile to volume, shake well, filter, and obtain the sample solution. S2. Chromatographic determination: The sample solution is injected into a high-performance liquid chromatograph equipped with an ultraviolet detector for detection, and the chromatogram is recorded; wherein, the chromatographic conditions for the high-performance liquid chromatography are: Column: C18 stainless steel column packed with octadecylsilane-bonded silica gel; Mobile phase: a mixed solution of acetonitrile and potassium dihydrogen phosphate aqueous solution; wherein the mass percentage concentration of the potassium dihydrogen phosphate aqueous solution is 0.1%; and the volume ratio of acetonitrile to potassium dihydrogen phosphate aqueous solution is 70:30~80:

20. Flow rate: 1.0 mL / min; Column temperature: 40℃; Detection wavelength: 230nm; Injection volume: 1.0 μL; Elution method: isocratic elution; S3. Content Calculation: The content of ethyltriphenylphosphine bromide and the residual amount of triphenylphosphine impurities are calculated using the area normalization method.

2. The method for determining the content of ethyltriphenylphosphine bromide according to claim 1, characterized in that: The potassium dihydrogen phosphate aqueous solution was prepared by dissolving 1.0 g of potassium dihydrogen phosphate in 1000 mL of water and shaking well.

3. The method for determining the content of ethyltriphenylphosphine bromide according to claim 1, characterized in that: The chromatographic column has a size of 250 mm × 4.6 mm and a packing particle size of 5 μm.

4. The method for determining the content of ethyltriphenylphosphine bromide according to claim 1, characterized in that: The volume ratio of the acetonitrile and potassium dihydrogen phosphate aqueous solution is 70:

30.

5. The method for determining the content of ethyltriphenylphosphine bromide according to claim 1, characterized in that: The volume ratio of the acetonitrile and potassium dihydrogen phosphate aqueous solution is 80:

20.

6. The method for determining the content of ethyltriphenylphosphine bromide according to claim 1, characterized in that: In S2, the running time for the chromatographic determination is 30.0 min.

7. The method for determining the content of ethyltriphenylphosphine bromide according to claim 1, characterized in that: In S1, 0.1 g of ethyltriphenylphosphine bromide sample is weighed and placed in a 25 mL volumetric flask and diluted to volume.

8. The method for determining the content of ethyltriphenylphosphine bromide according to claim 1, characterized in that: In S1, the duration of the ultrasonic oscillation is 5 minutes.

9. The method for determining the content of ethyltriphenylphosphine bromide according to claim 1, characterized in that: In S1, the filtration uses a filter membrane with a pore size of 0.45 μm.

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