Method for detecting N, N-diethylethylenediamine ion chromatography content in metoclopramide hydrochloride bulk drug

Abstract

The invention belongs to the technical field of medicine detection, and particularly relates to a method for detecting the ion chromatography content of N, N-diethylethylenediamine in a metoclopramide hydrochloride raw material medicine. The ion chromatography content detection method for the N, N-diethylethylenediamine in the metoclopramide hydrochloride bulk drug comprises the following chromatographic conditions: an electrical conductivity detector and a cation chromatographic column are adopted, the column temperature is 32-38 DEG C, the column flow is 0.7 mL / min-0. 9 mL / min, methane sulfonic acid with the concentration of 18 mmol / L-22 mmol / L is used as an eluent, and isocratic elution is performed for 15-30 min. The ion chromatography content detection method for the N, N-diethylethylenediamine in the metoclopramide hydrochloride bulk drug, provided by the invention, has the advantages of simplicity, convenience, rapidness, strong specificity, high accuracy and high sensitivity, and the drug safety is improved.

Description

Technical Field

[0001] The invention belongs to the technical field of drug detection, and particularly relates to an ion chromatography content detection method for N,N-diethylethylenediamine in a metoclopramide hydrochloride raw material drug. Background Art

[0002] Metoclopramide Hydrochloride, as a highly effective antiemetic drug, has significant clinical application value, especially in relieving nausea and vomiting symptoms caused by chemotherapy, radiotherapy and postoperative causes. Due to its wide application prospects and definite therapeutic effects, the quality control of metoclopramide hydrochloride is particularly important, which is directly related to the safety and effect of patient treatment.

[0003] In the preparation process of metoclopramide hydrochloride, N,N-diethylethylenediamine plays an indispensable role as a key starting material. The structural formula of N,N-diethylethylenediamine is . However, the problem of the residue of this material in raw materials cannot be ignored. Studies have shown that even trace residues may cause a series of adverse reactions, including but not limited to headaches, dizziness, nausea and vomiting, which seriously affect the safety of drugs and the quality of life of patients. Therefore, strict control of the content of N,N-diethylethylenediamine in raw materials is a key link in ensuring drug quality.

[0004] Traditionally, for impurities with ultraviolet absorption characteristics, high performance liquid chromatography (HPLC) has been widely used due to its high sensitivity, high resolution and easy operation. However, the ultraviolet absorption of N,N-diethylethylenediamine is weak, making HPLC incapable of detecting its content. Therefore, gas chromatography (GC) has become an alternative. GC has the advantages of high separation efficiency, fast analysis speed and good selectivity, and is especially suitable for volatile and thermally stable compounds. However, in the preparation process of metoclopramide hydrochloride, N,N-diethylethylenediamine will undergo a hydrochloric acid salt reaction and be converted into a hydrochloride form that is not easily vaporized, thereby limiting the application of GC.

[0005] At present, domestic and foreign pharmacopoeias such as USP (United States Pharmacopoeia), EP (European Pharmacopoeia) and BP (British Pharmacopoeia) have included metoclopramide hydrochloride, but in their quality standards, the control of N,N-diethylethylenediamine mainly relies on thin layer chromatography (TLC). Although the TLC method is simple to operate, it has limitations such as high operational complexity, poor specificity, low sensitivity and inability to accurately quantify, making it difficult to meet the high standards of modern drug quality control.

[0006] Therefore, in view of the importance of N,N-diethylethylenediamine in metoclopramide hydrochloride raw materials and the limitations of existing detection methods, developing a simple, accurate and sensitive method for detecting the content of N,N-diethylethylenediamine is of great significance for improving the quality control level of metoclopramide hydrochloride raw materials and ensuring the safety of patients' medication. Summary of the invention

[0007] The technical problem to be solved by the present invention is to overcome the above-mentioned defects in the prior art and provide an ion chromatography method for detecting the content of N,N-diethylethylenediamine in a metoclopramide hydrochloride raw material drug, which is simple, rapid, highly specific, accurate and sensitive, and improves the safety of the drug.

[0008] The ion chromatography content detection method of N,N-diethylethylenediamine in the metoclopramide hydrochloride raw material of the present invention comprises the following chromatographic conditions: using a conductivity detector, a cation chromatography column, a column temperature of 32-38° C., a column flow rate of 0.7 mL / min-0.9 mL / min, 18 mmol / L-22 mmol / L methane sulfonic acid as an eluent, and isocratic elution for 15-30 min. The preferred concentration of the eluent is 20 mmol / L.

[0009] The chromatographic conditions also include: the injection volume is 20-25 μL.

[0010] The cation chromatography column is Dionex IonPac TM CS17, 4mm×250mm.

[0011] Chromatographic conditions also include: Guard column: Dionex IonPac TM CG17, 4mm×50mm.

[0012] Also included are the following solution preparation and testing: 1) Preparation of reference solution: Reference solution: Take N,N-diethylethylenediamine reference, weigh accurately, add solvent to dissolve and dilute quantitatively; 2) Preparation of test solution: Test solution: Take a sample of metoclopramide hydrochloride bulk drug substance, accurately weigh it, add solvent to dissolve it and dilute it quantitatively; 3) Detection: The solvent, reference solution and test solution are accurately measured respectively, injected into an ion chromatograph, and the chromatogram is recorded; the chromatographic peak in the chromatogram of the test solution with the same retention time as the reference solution is calculated by the peak area according to the external standard method to obtain the content of N,N-diethylethylenediamine.

[0013] The solvent is water.

[0014] The detection limit of N,N-diethylethylenediamine detected by this method is 0.150μg / mL, and the quantification limit is 0.499μg / mL.

[0015] The detection range of this method for N,N-diethylethylenediamine is 0.479µg / mL~19.146µg / mL, and the linear equation is y=0.0339x-0.0095, R 2 =0.999.

[0016] Compared with the prior art, the present invention has the following beneficial effects: The ion chromatography content detection method of N,N-diethylethylenediamine in the metoclopramide hydrochloride raw material drug of the present invention has high sensitivity, good separation degree and strong specificity, and can accurately qualitatively and quantitatively detect the content of N,N-diethylethylenediamine in the metoclopramide hydrochloride raw material drug. Compared with the TLC method reported in the USP / EP / BP pharmacopoeia, it can more objectively, accurately and comprehensively evaluate the quality of the metoclopramide hydrochloride raw material drug, and has important practical significance for the control of product quality. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 This is the ion chromatogram of the solvent water in Example 1.

[0018] Figure 2 This is the ion chromatogram of the impurity N,N-diethylethylenediamine localization solution in Example 1.

[0019] Figure 3 It is the ion chromatogram of the test solution in Example 1.

[0020] Figure 4 This is the ion chromatogram of the spiked solution in Example 1.

[0021] Figure 5 This is the linear regression curve of the N,N-diethylethylenediamine line in Example 4.

[0022] Figure 6 This is the TLC chart of N,N-diethylethylenediamine content detection by thin layer chromatography in Comparative Example 1.

[0023] Figure 7 This is the chromatogram of N,N-diethylethylenediamine detected by gas chromatography in Comparative Example 2.

[0024] Figure 8 This is the ion chromatogram for detecting N,N-diethylethylenediamine in Comparative Example 3.

[0025] Fig. 9 This is the ion chromatogram for detecting N,N-diethylethylenediamine in Comparative Example 4. DETAILED DESCRIPTION

[0026] The present invention will be further described below in conjunction with specific embodiments.

[0027] The ion chromatography content detection method of N,N-diethylethylenediamine in the metoclopramide hydrochloride raw material of the present invention is that the metoclopramide hydrochloride raw material used is the raw material produced by Shandong Qidu Pharmaceutical Co., Ltd., and the N,N-diethylethylenediamine reference substance comes from the China Food and Drug Inspection Institute. A DIONEXICS-6000 ion chromatograph and a conductivity detector are used. The column temperature is 32-38°C, the column flow rate is 0.7mL / min-0.9mL / min, the injection volume is 20-25µL, 18mmol / L-22mmol / L methanesulfonic acid is used as the eluent, and the elution is isocratic. Chromatographic column: DionexIonPac TM CS17, 4mm×250mm, guard column: Dionex IonPac TM CG17, 4mm×50mm.

[0028] Preferably, the eluent is 20 mmol / L methanesulfonic acid. At this concentration, the method is more optimal.

[0029] Preferably, the gradient elution conditions are: isocratic elution for 15-30 min, with the 15 min method being more preferred.

[0030] Preferably, the eluent flow rate is 0.7 mL / min-0.9 mL / min.

[0031] Preferably, the injection volume is 20-25 µL.

[0032] The preferred detection method comprises the following steps: 1) Preparation of reference solution: Reference solution: Take an appropriate amount of N,N-diethylethylenediamine reference, weigh accurately, dissolve in solvent and quantitatively dilute to make a solution of 10µg per 1mL; 2) Preparation of test solution: Test solution: Take an appropriate amount of metoclopramide hydrochloride bulk drug, accurately weigh it, dissolve it in solvent and quantitatively dilute it to make a solution containing 5 mg per 1 mL; 3) Detection: Accurately measure the solvent, reference solution and test solution respectively, inject them into the ion chromatograph, and record the chromatogram; if there is a chromatographic peak in the chromatogram of the test solution with the same retention time as the reference solution, calculate the content of N,N-diethylethylenediamine by peak area according to the external standard method.

[0033] Preferably, in the above method, the solvent used in preparing the solution is water.

[0034] The characteristic value content of N,N-diethylethylenediamine used in the following examples and comparative examples is C6H 16 N2 is 96.0%.

[0035] Example 1 The specificity experiment of the ion chromatography content detection method of N, N-diethylethylenediamine in the above metoclopramide hydrochloride raw material: (1) Preparation of impurity N,N-diethylethylenediamine localization solution: Accurately weigh 50 mg of N,N-diethylethylenediamine (EP impurity E) reference substance, place it in a 50 mL volumetric flask, dilute to the mark with solvent water, shake well to obtain reference substance stock solution, accurately measure 1 mL of reference substance stock solution, place it in a 100 mL volumetric flask, add diluent to dilute to the mark, and shake well.

[0036] (2) Preparation of test solution: Accurately weigh 50 mg of metoclopramide hydrochloride bulk drug substance, place in a 10 mL volumetric flask, add water to dissolve and dilute to the scale, and shake well.

[0037] (3) Preparation of spiked solution: Accurately weigh 50 mg of metoclopramide hydrochloride API and place it in a 10 mL volumetric flask. Add the impurity N,N-diethylethylenediamine (EP impurity E) fixation solution to dissolve and dilute to the scale, and shake well.

[0038] (4) Accurately measure the solvent water, impurity N,N-diethylethylenediamine positioning solution, test solution, and spiked solution respectively, inject them into the ion chromatograph, and detect them under the following chromatographic conditions. Record the chromatograms. The chromatograms of the solvent water, impurity N,N-diethylethylenediamine positioning solution, test solution, and spiked solution are as follows: Figure 1 , Figure 2 , Figure 3 , Figure 4 If there is a chromatographic peak in the chromatogram of the test solution with the same retention time as the impurity N,N-diethylethylenediamine positioning solution, the content of N,N-diethylethylenediamine is calculated by peak area according to the external standard method. The results are shown in Table 1.

[0039] The chromatographic conditions used were: ion chromatograph: DIONEXICS-6000; detector: conductivity detector; chromatographic column: DionexIonPac TM , CS17, 4mm×250mm; Guard column: Dionex IonPac TM CG17, 4mm×50mm; eluent: 0.02mol / L methanesulfonic acid aqueous solution; isocratic elution: 15min; flow rate: 0.8mL / min; column temperature: 35℃; constant temperature box: 30℃; cell temperature: 30℃; injection volume: 25µL.

[0040] Table 1 Specificity test results

[0041] Conclusion: Figure 1-4 As can be seen from Table 1, solvent water as a blank solvent does not interfere with the detection of N,N-diethylethylenediamine; no other interfering peaks appear at the retention position of the N,N-diethylethylenediamine peak in the test solution, and the method has good specificity.

[0042] Example 2 System precision experiment of the above method for detecting the content of N,N-diethylethylenediamine in the metoclopramide hydrochloride raw material: (1) Preparation of N,N-diethylethylenediamine reference stock solution: Accurately weigh 50 mg of N,N-diethylethylenediamine reference substance, place in a 50 mL volumetric flask, dilute to scale with solvent water, shake well, and prepare reference substance stock solution; (2) Preparation of N,N-diethylethylenediamine reference solution: Accurately measure 1 mL of reference stock solution, place in a 100 mL volumetric flask, add solvent water to dilute to the mark, and shake well.

[0043] (3) According to the chromatographic conditions of Example 1, the N,N-diethylethylenediamine reference solution was accurately measured and injected in parallel for 6 times, injected into the ion chromatograph for detection, and the chromatogram was recorded. The relative standard deviation (RSD) of the peak area and retention time of each peak of the reference solution injected 6 times was calculated. The results are shown in Table 2.

[0044] Table 2 System precision test results

[0045] Conclusion: It can be seen from Table 2 above that the reference solution was injected 6 times continuously, the RSD of the reference peak area was 2.4%, less than 10.0%, and the RSD of the retention time was 0.1%, less than 1.0%, indicating that the system precision of the method of the present invention is good.

[0046] Example 3 The detection limit / quantification limit experiment of the ion chromatography content detection method of N,N-diethylethylenediamine in the above metoclopramide hydrochloride raw material: (1) Using solvent water as blank, adjust the instrument sensitivity, inject samples three times continuously, record the instrument noise level within the peak time range of the analyte, and calculate the average baseline noise peak height. The results are shown in Table 3.

[0047] (2) Limit of quantification: Quantitative limit solution: Accurately measure 0.5 mL of the impurity N,N-diethylethylenediamine positioning solution in Example 1, place it in a 10 mL volumetric bottle, add solvent water to dilute to the scale, and shake well. Inject 6 times continuously. The ratio of the average peak height of 6 needles to the average baseline noise peak height (S / N) should be greater than 10. The results are shown in Table 5.

[0048] (3) Detection limit: Detection limit solution: Accurately measure 3.0 mL of "quantification limit solution" and place it in a 10 mL volumetric bottle. Add solvent water to dilute to the scale and shake well. Inject three times continuously. The ratio (S / N) of the average peak height of the three needles to the average baseline noise peak height should be greater than 3. The results are shown in Table 4.

[0049] (4) According to the chromatographic conditions of Example 1, the solvent water, quantitative limit solution, and detection limit solution were accurately measured and injected respectively. The solvent water was injected in parallel for 3 times, the detection limit solution was injected in parallel for 3 times, and the quantitative limit solution was injected in parallel for 6 times. The chromatogram was recorded and the RSD of the peak area of ​​the quantitative limit solution was calculated. The results are shown in Table 5.

[0050] Table 3 Baseline noise results

[0051] Table 4 Detection limit results of N,N-diethylethylenediamine

[0052] Table 5 Quantification limit results of N,N-diethylethylenediamine

[0053] Conclusion: From the results of the detection limit and quantification limit experiments in Tables 3 to 5 above, it can be seen that in the method of the present invention, the detection limit concentration of the impurity N,N-diethylethylenediamine is 0.144 μg / mL, equivalent to 0.003% of the test sample concentration; the quantification limit concentration is 0.479 μg / mL, equivalent to 0.010% of the test sample concentration, so the method of the present invention has high sensitivity.

[0054] Example 4 The linear experiment of the ion chromatography content detection method of N,N-diethylethylenediamine in the above metoclopramide hydrochloride raw material: (1) Determine the linear relationship between the response value of N,N-diethylethylenediamine and its concentration within a certain range from the quantitative limit concentration to the detection concentration.

[0055] (2) Linear stock solution: Take the reference stock solution in Example 2 as the linear stock solution; Linear solution 1: Accurately measure 0.2 mL of the linear stock solution, place it in a 100 mL volumetric flask, add solvent water to dilute to the scale, shake well, and obtain.

[0056] Linear solution 2: Accurately measure 0.5 mL of the linear stock solution, place it in a 100 mL volumetric flask, add solvent water to dilute to the scale, shake well, and obtain.

[0057] Linear solution 3: Accurately measure 0.8 mL of the linear stock solution, place it in a 100 mL volumetric flask, add solvent water to dilute to the scale, shake well, and obtain.

[0058] Linear solution 4: Accurately measure 1 mL of the linear stock solution, place it in a 100 mL volumetric flask, add solvent water to dilute to the scale, shake well, and obtain.

[0059] Linear solution 5: Accurately measure 1.5 mL of the linear stock solution, place it in a 100 mL volumetric flask, add solvent water to dilute to the scale, shake well, and obtain.

[0060] (3) Quantitation limit solution: The quantitation limit solution result of Example 3 was used (concentration 0.479 µg / mL; peak area 0.012).

[0061] (4) According to the chromatographic conditions of Example 1, accurately measure the above linear solutions 1, 2, 3, 4, and 5, inject them respectively, and record the chromatogram. With the sample concentration as the abscissa and the corresponding peak area as the ordinate, draw a linear regression curve of the N,N-diethylethylenediamine line, as shown in FIG. Figure 5 The regression equation and the corresponding linear regression coefficient are calculated as shown in Table 6. The linear experimental results of N,N-diethylethylenediamine line are shown in Table 6.

[0062] Table 6 N,N-diethylethylenediamine linear test results

[0063] Conclusion: From Table 6 above, it can be seen that in the range of 0.479µg / mL~19.146µg / mL, the linear equation of N,N-diethylethylenediamine is y=0.0339x-0.0095, and the correlation coefficient is 1.0000, which meets the requirements and has a good linear relationship.

[0064] Example 5 The accuracy experiment of the above-mentioned N, N-diethylethylenediamine ion chromatography content detection method in the metoclopramide hydrochloride raw material: (1) Determine the difference between the measurement results of the chromatographic method within the expected range (quantitation limit ~ 150% of the limit concentration) and the true value. This confirms whether the method can obtain accurate test results.

[0065] (2) Reference stock solution: Accurately weigh 50 mg of N,N-diethylethylenediamine reference substance into a 50 mL volumetric flask, dilute to the mark with solvent water, and shake well.

[0066] (3) Reference solution (100% concentration reference solution): Accurately measure 1 mL of reference stock solution, place in a 100 mL volumetric flask, add solvent water to dilute to the mark, and shake well.

[0067] 20% concentration reference substance solution: Accurately measure 0.2 mL of reference substance stock solution, place in a 100 mL volumetric flask, add diluent to dilute to the scale, shake well, and obtain.

[0068] 50% concentration reference substance solution: Accurately measure 0.5 mL of reference substance stock solution, place in a 100 mL volumetric flask, add diluent to dilute to the scale, shake well, and obtain.

[0069] 150% concentration reference substance solution: Accurately measure 1.5 mL of reference substance stock solution, place in a 100 mL volumetric flask, add diluent to dilute to the scale, shake well, and obtain.

[0070] (4) Blank sample solution: Accurately weigh about 50 mg of metoclopramide hydrochloride raw material, place in a 10 mL volumetric flask, add solvent water to dissolve and dilute to scale, shake well, and prepare 3 more in the same way.

[0071] 50% concentration accuracy solution: accurately weigh 50 mg of the test sample, place it in a 10 mL volumetric bottle, add 50% concentration reference solution to dissolve and dilute to the scale, shake well, and prepare 3 portions in the same way.

[0072] 100% concentration accuracy solution: accurately weigh 50 mg of the test sample, place it in a 10 mL volumetric flask, add the reference solution (100% concentration reference solution) to dissolve and dilute to the scale, shake well, and the solution is ready. Prepare 3 portions in the same way.

[0073] 150% concentration accuracy solution: accurately weigh 50 mg of the test sample, place it in a 10 mL volumetric flask, add 150% concentration reference solution to dissolve and dilute to the scale, shake well, and prepare 3 portions in the same way.

[0074] 20% concentration accuracy solution: accurately weigh 50 mg of the test sample, place it in a 10 mL volumetric bottle, add 20% concentration reference solution to dissolve and dilute to the scale, shake well, and prepare 3 portions in the same way.

[0075] (5) According to the chromatographic conditions of Example 1, accurately measure each of the above solutions, inject them respectively, and record the chromatogram. The recovery rate of the 20% concentration accuracy solution should be between 70% and 130%, and the recovery rate of other concentrations should be between 80% and 120%. The results are shown in Table 7.

[0076] Table 7 N,N-diethylethylenediamine accuracy test results

[0077] Conclusion: The recovery rate of the impurity at 50%-150% concentration was 95.2%-115.8%, between 80% and 120%, and the recovery rate at 20% concentration was 107.9%, between 70% and 130%. Both met the requirements and the method had good accuracy.

[0078] Example 6 The durability experiment of the above-mentioned N, N-diethylethylenediamine ion chromatography content detection method in the metoclopramide hydrochloride raw material: Taking the chromatographic conditions of Example 1 as standard conditions, it was determined that the N,N-diethylethylenediamine determination method was still robust when the chromatographic conditions changed as follows.

[0079] (1) The injection volume was changed to 20 μL, and the other conditions were the same as those in the steps and Example 1; (2) Changing the column temperature to 32°C and 38°C respectively, and other conditions were the same as those in step 1; (3) The flow rates were changed to 0.7 mL / min and 0.9 mL / min respectively, and the other conditions were the same as those in step 1; (4) Changing the concentration of the eluent to 18 mmol and 22 mmol respectively, the other conditions were the same as those in step 1; After the chromatographic conditions were changed, the corresponding experimental results are shown in Table 8. When the impurity content is less than 0.05% (the relative change rate under standard conditions is not calculated); the impurity content is between 0.05% and 0.10% (the relative change rate under standard conditions is less than 50%); the impurity content is between 0.11% and 0.50% (the relative change rate under standard conditions is less than 30%).

[0080] Table 8 Durability test results

[0081] Conclusion: When the chromatographic conditions change slightly, the maximum relative change rate compared with the standard conditions is 8.7%, which is less than 30%, meeting the requirements. Therefore, the method of the present invention has good durability.

[0082] Comparative Example 1 The chromatographic conditions of this comparative example are different from those of the embodiment in that the chromatographic method is TLC. The EP Pharmacopoeia metoclopramide hydrochloride bulk drug quality standard uses TLC to detect this impurity, but this method can only perform limit detection, and has complex operation, low sensitivity, and poor specificity. The limit spot is extremely unclear, such as Figure 6 As shown, it is not suitable for the quantitative detection of N,N-diethylethylenediamine.

[0083] Comparative Example 2 The chromatographic conditions of this comparative example are different from those of the embodiment in that the chromatographic method is GC. N,N-diethylethylenediamine is a low-boiling impurity and can be detected by GC. However, the metoclopramide hydrochloride raw material process undergoes a hydrochloride salt-forming reaction, and the impurity will be derived into N,N-diethylethylenediamine hydrochloride, which cannot be vaporized. Therefore, GC is not applicable. Figure 7 As shown, no clear target peak was detected in the spiked test solution, and the GC method was not applicable.

[0084] Comparative Example 3 The chromatographic conditions of this comparative example are different from those of the embodiment only in that the chromatographic column is Dionex Ion PacTM CS12A, 4 mm × 250 mm. Under this method, the chromatographic peak of N, N-diethylethylenediamine reference substance is not retained and is eluted within 1 min. The method is applicable, such as Figure 8 shown.

[0085] Comparative Example 4 The chromatographic conditions of this comparative example are different from those of the embodiment only in that the eluent is 8 mmol methanesulfonic acid-acetonitrile (volume ratio 85:15). Under this method, there is an inverted peak at the chromatographic peak position of N,N-diethylethylenediamine, such as Fig. 9 As shown. It is well known that the ion chromatography suppressor cannot contact the organic phase. To meet the above method, the instrument needs to be equipped with an external water device, and the gas pressure needs to control the flow rate under this condition, which has a large error and will lead to poor system precision. The premise of using this method is that the experimenter is very familiar with the various structures of the instrument, otherwise it is very easy to cause damage to the suppressor. This method is not suitable for continued use.

Claims

1. A method for detecting the content of N,N-diethylethylenediamine in metoclopramide hydrochloride bulk drug by ion chromatography, characterized in that: The chromatographic conditions include: a conductivity detector, a cation chromatography column, a column temperature of 32-38°C, a column flow rate of 0.7mL / min-0.9mL / min, 18mmol / L-22mmol / L methanesulfonic acid as the eluent, and isocratic elution.

2. The method for detecting the content of N,N-diethylethylenediamine by ion chromatography in the metoclopramide hydrochloride bulk drug according to claim 1, characterized in that: The chromatographic conditions also include: the injection volume is 20-25 μL.

3. The method for detecting the content of N,N-diethylethylenediamine by ion chromatography in the metoclopramide hydrochloride bulk drug according to claim 1, characterized in that: The cation chromatography column is Dionex IonPac TM CS17.

4. The method for detecting the content of N,N-diethylethylenediamine by ion chromatography in the metoclopramide hydrochloride bulk drug according to claim 1, characterized in that: Chromatographic conditions also include: Guard column: Dionex IonPac TM CG17.

5. The method for detecting the content of N,N-diethylethylenediamine by ion chromatography in the metoclopramide hydrochloride bulk drug according to claim 1, characterized in that: Also included are the following solution preparation and testing: 1) Preparation of reference solution: Reference solution: Take N,N-diethylethylenediamine reference, weigh accurately, add solvent to dissolve and dilute quantitatively; 2) Preparation of test solution: Test solution: Take a sample of metoclopramide hydrochloride bulk drug substance, accurately weigh it, add solvent to dissolve it and dilute it quantitatively; 3) Detection: The solvent, reference solution and test solution are accurately measured respectively, injected into an ion chromatograph, and the chromatogram is recorded; the chromatographic peak in the chromatogram of the test solution with the same retention time as the reference solution is calculated by the peak area according to the external standard method to obtain the content of N,N-diethylethylenediamine.

6. The method for detecting the content of N,N-diethylethylenediamine by ion chromatography in the metoclopramide hydrochloride bulk drug according to claim 5, characterized in that: The solvent is water.

7. The method for detecting the content of N,N-diethylethylenediamine by ion chromatography in the metoclopramide hydrochloride bulk drug according to claim 1, characterized in that: The detection limit of N,N-diethylethylenediamine detected by this method is 0.150μg / mL, and the quantification limit is 0.499μg / mL.

8. The method for detecting the content of N,N-diethylethylenediamine by ion chromatography in the metoclopramide hydrochloride bulk drug according to claim 1, characterized in that: The detection range of this method for N,N-diethylethylenediamine is 0.479µg / mL~19.146µg / mL, and the linear equation is y=0.0339x-0.0095, R 2 =0.999.

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