Method for detecting glucose residue in irinotecan hydrochloride liposome injection

Abstract

The invention relates to the technical field of drug analysis and detection, and particularly discloses a method for detecting the residual quantity of glucose in an irinotecan hydrochloride liposome injection. According to the method, irinotecan hydrochloride in the liposome is fully separated from small molecular substances such as glucose and sodium chloride by adopting an ultrafiltration method, then, a Waters XBridge BEH HILIC chromatographic column is adopted, a mixed solution of an acetate buffer solution with the pH value of 3.8-4.2 and acetonitrile is used as a mobile phase, and the content of irinotecan hydrochloride in the liposome is detected in an isocratic elution mode by adopting a high performance liquid chromatography method. The effective separation of glucose, sodium chloride, 4-hydroxyethylpiperazine, sucrose octasulfate potassium and other substances is realized, and the condition of the glucose residue in the irinotecan hydrochloride liposome is accurately detected. The invention provides a reliable guarantee for improving and better controlling the quality of the irinotecan hydrochloride liposome injection product, and has very important significance for improving the medication safety.

Description

Technical Field

[0001] The invention relates to the technical field of drug analysis and detection, and in particular to a method for detecting residual glucose in irinotecan hydrochloride liposome injection. Background Art

[0002] Irinotecan (CPT-11), chemically named (+)-(4S)-4,11-diethyl-4-hydroxy-9[(4-piperidinylpiperidine)carbonyl]-1H-pyrano[3',4':6,7]indolizine[1,2-b]quinoline-3,14-(4H,12H)-dione hydrochloride trihydrate, is a semi-synthetic derivative of camptothecin and an effective drug for the treatment of metastatic colon cancer. Irinotecan hydrochloride is the hydrochloride of irinotecan and has good water solubility. Currently, the irinotecan products on the market include irinotecan hydrochloride injection, lyophilized powder injection and liposome injection.

[0003] As a drug carrier that has been widely studied in recent years, liposomes are mainly characterized by protecting encapsulated drugs, increasing drug stability, changing the distribution behavior of drugs in the body, and carrying drugs to passively or actively target the lesion site. As a good carrier of anti-tumor drugs, liposomes can effectively improve the efficacy of drugs and reduce toxic side effects. Therefore, irinotecan hydrochloride liposome injection has been widely used in clinical practice. In October 2015, the FDA approved the irinotecan liposome drug Onivyde for the treatment of advanced pancreatic cancer. The raw materials and excipients for the preparation of irinotecan hydrochloride liposome injection on the market mainly include irinotecan hydrochloride, sodium chloride, glucose, 4-hydroxyethylpiperazine and sucrose octasulfate potassium. Residual glucose is easily degraded into 5-methylfurfural in irinotecan hydrochloride liposome injection, which affects the quality and safety of the product. Therefore, it is necessary to control the content of residual glucose in irinotecan hydrochloride liposome injection. However, the pharmacopoeias of various countries have not yet included the detection method of residual glucose content in irinotecan hydrochloride liposome injection. Therefore, developing a method for detecting the residual glucose content in irinotecan hydrochloride liposome injection is of great significance for improving the quality control of irinotecan hydrochloride liposome injection and improving the safety of patient medication. Summary of the invention

[0004] In view of the above technical problems, the present invention provides a method for detecting the residual glucose in irinotecan hydrochloride liposome injection.

[0005] In order to solve the above technical problems, the technical solution provided by the present invention is: A method for detecting the residual glucose in irinotecan hydrochloride liposome injection, using high performance liquid chromatography for detection, comprises the following steps: (1) Preparation of test solution and mixed reference solution: Preparation of reference solution: Take glucose reference and prepare mixed reference solution with water; Preparation of test solution: Take a sample of irinotecan hydrochloride liposome injection and add water, mix well, ultrafilter, and centrifuge to obtain the test solution; (2) Take the reference solution and the test solution and perform the test according to the following liquid chromatography conditions: Column: Waters XBridge BEH HILIC, 250 mm × 4.6 mm, 5 µm; ELSD detector; Mobile phase: a mixed solution of acetate buffer and acetonitrile at pH 3.8-4.2, wherein the volume ratio of acetate buffer to acetonitrile is (88-92): (12-8); The elution mode was isocratic.

[0006] Compared with the prior art, the method for detecting the residual glucose in irinotecan hydrochloride liposome injection provided by the present invention adopts ultrafiltration to fully separate irinotecan hydrochloride from small molecules such as glucose and sodium chloride in liposomes, and then adopts Waters XBridge BEH HILIC (250mm×4.6mm, 5µm) chromatographic column, takes a mixed solution of acetate buffer solution with pH 3.8-4.2 and acetonitrile as mobile phase, and uses high performance liquid chromatography in an isocratic elution manner to achieve effective separation of substances such as glucose, sodium chloride, 4-hydroxyethylpiperazine and sucrose octasulfate potassium, and accurately detects the residual glucose in irinotecan hydrochloride liposomes. Moreover, the method provided by the present invention has been studied and verified through methodological studies on specificity, sensitivity and the like, and it is found that the method provided by the present invention has good sensitivity, accuracy and reproducibility, and can realize accurate quantitative detection of the residual glucose amount in irinotecan hydrochloride liposomes in a simple and quick way, thus solving the problem that the prior art cannot accurately quantitatively detect the residual glucose amount in irinotecan hydrochloride liposomes, providing a reliable guarantee for improving and better controlling the quality of irinotecan hydrochloride liposome injection products, and also having a very important significance for improving the safety of medication.

[0007] Preferably, the volume ratio of acetate buffer to acetonitrile in the mobile phase is 90:10.

[0008] During the experiment, the inventors found that glucose and the adjacent impurity peak sodium chloride could not be effectively separated, and the column efficiency of glucose on the chromatographic column was low. Through creative thinking, the inventors used a mixed solution of acetate buffer and acetonitrile at a specific ratio of pH 3.8-4.2 as the mobile phase, selected Waters XBridge BEH HILIC (250mm×4.6mm, 5µm) as the detection column, and achieved effective separation of glucose, sodium chloride, 4-hydroxyethylpiperazine and sucrose octasulfate potassium through isocratic elution, which is conducive to the accurate qualitative and quantitative detection of glucose residues in irinotecan hydrochloride liposome products, and facilitates more accurate monitoring of the quality of irinotecan hydrochloride liposome products.

[0009] Preferably, the pH of the acetate buffer is 4.0.

[0010] The preferred pH value of the acetate buffer can reduce spectral band tailing and improve peak shape, thereby facilitating improved separation between components and making the detection results more accurate and precise.

[0011] Furthermore, the preparation method of the acetate buffer comprises the following steps: taking 1.542 g of ammonium acetate, adding 1000 mL of purified water to dissolve, adjusting the pH to 4.0 with glacial acetic acid, shaking well, filtering, and obtaining the acetate buffer.

[0012] Preferably, the column temperature is 38°C to 42°C.

[0013] More preferably, the column temperature is 40°C.

[0014] Preferably, the flow rate is 0.8 mL / min to 1.2 mL / min.

[0015] More preferably, the flow rate is 1.0 mL / min.

[0016] Preferably, the injection volume is 10 μL.

[0017] The preferred detection conditions can achieve a higher separation degree between glucose and various impurities to ensure the effective detection of impurities, thereby achieving the purpose of effectively and accurately controlling the residual glucose content in the irinotecan hydrochloride liposome product.

[0018] Furthermore, the preparation of the test solution specifically includes the following steps: taking an irinotecan hydrochloride liposome injection sample, adding 1.8 to 2.2 times the volume of purified water, mixing evenly, ultrafiltration, and centrifugation to obtain a test solution.

[0019] Furthermore, the ultrafiltration membrane used in the ultrafiltration has a molecular weight cutoff of 9.5 KDa to 10.5 kDa.

[0020] Furthermore, the centrifugal speed is 4500g~5500g, and the centrifugal time is 50min~90min.

[0021] The preferred method for preparing the test solution can ensure that small molecular components such as glucose and sodium chloride are completely separated, and at the same time, can ensure that the encapsulated irinotecan hydrochloride is not destroyed, so as to ensure the accuracy of the test results.

[0022] The detection method provided by the present invention can realize the effective separation of irinotecan hydrochloride, glucose and sodium chloride, 4-hydroxyethylpiperazine, sucrose octasulfate potassium and other substances, accurately qualitatively and quantitatively detect the residual glucose in irinotecan hydrochloride liposome injection, which is beneficial to effectively control the quality of irinotecan hydrochloride liposome injection, and the operation is simple and fast with high sensitivity, which provides a simple and reliable method for the quality control of irinotecan hydrochloride liposome injection products, and at the same time, it is also beneficial to improve the drug safety of patients, and has high practical value. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 The chromatogram of the sodium chloride reference solution under the specificity item in Example 2; Figure 2 is the chromatogram of the glucose reference solution under the specificity item in Example 2; Figure 3 The chromatogram of the 4-hydroxyethylpiperazineethanesulfonic acid reference substance solution under the specificity item in Example 2; Figure 4 The chromatogram of the sucrose potassium octasulfate reference substance solution under the specificity item in Example 2; Figure 5 is a chromatogram of the irinotecan hydrochloride reference solution under the specificity item in Example 2; Figure 6 The chromatogram of the test solution spiked under the specificity item in Example 2; Figure 7 It is the chromatogram of the sodium chloride reference substance solution in Comparative Example 1; Figure 8 It is the chromatogram of the glucose reference solution in Comparative Example 1. DETAILED DESCRIPTION

[0024] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0025] Example 1 Materials and Methods Instruments: High performance liquid chromatograph, UV detector, volumetric flask, electronic balance.

[0026] Reagents: acetonitrile, ammonium acetate, purified water.

[0027] Blank solvent: purified water.

[0028] 1.1 Solution preparation Preparation of pH 4.0 acetate buffer: Take 1.542 g of ammonium acetate, add 1000 mL of purified water to dissolve, adjust the pH to 4.0 with glacial acetic acid, shake well, filter through a 0.45 μm filter membrane, and degas by ultrasonication to obtain acetate buffer.

[0029] Mobile phase: pH 4.0 acetate buffer and acetonitrile were mixed evenly in a volume ratio of 90:10, filtered through a 0.45 μm filter membrane, and ultrasonically degassed to obtain the mobile phase.

[0030] Grape reference sugar stock solution: Accurately weigh 40 mg of glucose reference, place in a 100 mL volumetric flask, add purified water to dissolve and dilute to the scale, mix thoroughly to make a glucose reference stock solution containing approximately 400 μg of glucose per 1 mL.

[0031] Preparation of reference solution 1: Accurately measure 2 mL of glucose stock solution, place it in a 20 mL volumetric flask, add purified water to dissolve and dilute to the scale, mix thoroughly to obtain reference solution 1.

[0032] Preparation of reference solution 2: Accurately measure 1.5 mL of glucose stock solution, place it in a 20 mL volumetric flask, add purified water to dissolve and dilute to the scale, mix thoroughly to obtain reference solution 2.

[0033] Preparation of reference solution 3: Accurately measure 1 mL of glucose stock solution, place it in a 20 mL volumetric flask, add purified water to dissolve and dilute to the scale, mix thoroughly to obtain reference solution 3.

[0034] Preparation of reference solution 4: Accurately measure 0.5 mL of glucose stock solution, place it in a 20 mL volumetric flask, add purified water to dissolve and dilute to the scale, mix thoroughly to obtain reference solution 4.

[0035] Preparation of reference solution 5: Accurately measure 0.2 mL of glucose stock solution, place it in a 20 mL volumetric flask, add purified water to dissolve and dilute to the scale, mix thoroughly to obtain reference solution 5.

[0036] Preparation of test solution: Take 5 mL of irinotecan hydrochloride liposome injection sample, place it in a 10 mL volumetric flask, add purified water to dilute to the scale, mix thoroughly, transfer all of the above solution to an ultrafiltration centrifuge tube (Amicon Ultra-15, 10 KDa), centrifuge at 5000g for 60 min at room temperature, take the solution after centrifugation to obtain the test solution.

[0037] System suitability requirements: The linear regression equation is calculated using the logarithmic values ​​of the concentrations of the series of reference solutions and the logarithmic values ​​of the corresponding main peak areas. The correlation coefficient (r) should be no less than 0.995; the recovery rate of the system suitability solution should be in the range of 98.0% to 102.0%.

[0038] 1.2 High performance liquid chromatography conditions: Column: Waters XBridge BEH HILIC, 250 mm × 4.6 mm, 5 µm; ELSD detector; Mobile phase: a mixed solution of acetate buffer at pH 4.0 and acetonitrile, wherein the volume ratio of acetate buffer to acetonitrile is 90:10; Flow rate: 1.0 mL / min; Column temperature, 40 °C; Injection volume: 10 μL; Isocratic elution; Running time: 30min.

[0039] The determination method is to take samples of a series of reference solution and test solution respectively, establish a linear equation for the reference solution by the least squares method, and calculate the content of glucose in the test solution.

[0040] Example 2 Methodological validation: 2.1 Exclusivity Glucose reference solution: Take about 1 mg of glucose reference, accurately weigh, place in a 10 mL volumetric flask, dissolve and dilute to the scale with purified water, shake well to obtain the glucose reference solution.

[0041] Sodium chloride reference solution: Take about 1 mg of sodium chloride reference, accurately weigh it, place it in a 10 mL volumetric flask, dissolve it with purified water and dilute it to the scale, shake well, and obtain the sodium chloride reference solution.

[0042] 4-Hydroxyethylpiperazineethanesulfonic acid reference solution: Take about 1 mg of 4-hydroxyethylpiperazineethanesulfonic acid reference, accurately weigh it, place it in a 10 mL volumetric flask, dissolve it with purified water and dilute it to the scale, shake it well, and obtain the 4-hydroxyethylpiperazineethanesulfonic acid reference solution.

[0043] Sucrose potassium octasulfate reference solution: Take about 1 mg of sucrose potassium octasulfate reference, accurately weigh, place in a 10 mL volumetric flask, dissolve and dilute to the scale with purified water, shake well to obtain sucrose potassium octasulfate reference solution.

[0044] Irinotecan hydrochloride reference solution: Take about 0.5 mg of irinotecan hydrochloride reference, accurately weigh, place in a 10 mL volumetric flask, add purified water to dissolve and dilute to the scale, shake well to obtain irinotecan hydrochloride reference solution.

[0045] Spiked test solution: Accurately measure 5 mL of irinotecan hydrochloride liposome injection sample, place it in a 20 mL volumetric flask, accurately add 2.5 mL of the above glucose reference stock solution, dilute to the mark with purified water, and mix thoroughly. Accurately measure 10 mL of the above solution into an ultrafiltration centrifuge tube (Amicon Ultra-15, 10 KDa), centrifuge at 5000 g for 90 min at 10 ° C, accurately measure 4 mL of the solution after centrifugation, place it in a 10 mL volumetric flask, dilute to the mark with acetonitrile, and mix thoroughly to obtain the spiked test solution.

[0046] Take each solution and test it according to the above HPLC conditions, record the chromatogram, among which the chromatographic peak of the sodium chloride reference solution is as follows: Figure 1 As shown in the figure, sodium chloride is two peaks, the two peaks in the figure are chloride ion (peak time is 3.951min) and sodium ion peak (peak time is 31.678min). The chromatographic peaks of glucose reference solution are as follows Figure 2 As shown in Figure 1, the peak time of glucose is 6.863 min. The chromatogram of 4-hydroxypiperazineethanesulfonic acid reference solution is as follows: Figure 3 As shown in FIG. 1 , 4-hydroxypiperazineethanesulfonic acid is two peaks, with the elution times being 25.686 min and 27.760 min. The chromatogram of the sucrose potassium octasulfate reference solution is shown in FIG. Figure 4 As shown in the figure, sucrose octasulfate potassium is 3 peaks, the elution time of sucrose octasulfate is 3.037min and 4.368min, and the elution time of potassium ion is 34.051min. The chromatogram of irinotecan hydrochloride reference solution is shown in the figure Figure 5 As shown in Figure 1, the peak time is 34.179 min. The chromatogram of the spiked test solution is shown in Figure 1. Figure 6 As shown in the figure, from left to right are the chromatographic peaks of chloride ion, glucose, sodium ion and 4-hydroxyethylpiperazine. Among them, the elution time of glucose is 6.871min.

[0047] The test results show that the chromatographic peaks introduced by sodium chloride, 4-hydroxyethylpiperazine, sucrose octasulfate potassium, irinotecan hydrochloride and other ingredients do not interfere with the detection of glucose peaks. The separation degree between the glucose peak and the adjacent chromatographic peaks in the spiked test solution is not less than 1.5, indicating that the method has good specificity.

[0048] 2.2 Limit of detection and limit of quantification Quantitation limit solution: Accurately measure 1 mL of reference solution 4 in Example 1, place in a 5 mL volumetric flask, dilute to the mark with purified water, and shake well to obtain the quantitation limit solution.

[0049] Detection limit solution: Accurately measure 1 mL of the reference solution 4 in Example 1, place it in a 10 mL volumetric flask, dilute to the mark with purified water, and shake well to obtain the detection limit solution.

[0050] The quantitative limit solution and the detection limit solution were tested according to the above-mentioned high performance liquid chromatography method, the quantitative limit solution was continuously injected 6 times, and the detection limit solution was continuously injected 3 times, and the chromatogram was recorded. The results are shown in Table 1.

[0051] Table 1

[0052] The results show that the relative standard deviation of the glucose peak area in the six quantitative limit solutions is no more than 10.0%. In the detection limit solution, the signal-to-noise ratio of the glucose peak is not less than 3.

[0053] 2.3 Precision Test solution: accurately measure 5 mL of irinotecan hydrochloride liposome injection sample, place it in a 10 mL volumetric flask, dilute to the mark with purified water, mix thoroughly, transfer all the solution to an ultrafiltration centrifuge tube (Amicon Ultra-15, 10 KDa), centrifuge at 5000 g for 90 min at 10 ° C, accurately measure 4 mL of the solution after centrifugation, place it in a 10 mL volumetric flask, dilute to the mark with acetonitrile, mix thoroughly, and prepare 6 copies in parallel. Detect according to the above-mentioned high performance liquid chromatography method, record the chromatogram, and the results are shown in Table 2.

[0054] Table 2 Precision

[0055] The test results show that the maximum absolute difference of the glucose content determination results in the 6 test solutions does not exceed 10µg / mL, proving that the precision of the method of the present invention is good.

[0056] 2.4 Accuracy Test sample spiked solution (120% concentration level): Accurately measure 5 mL of irinotecan hydrochloride liposome injection sample, place it in a 20 mL volumetric flask, accurately add 3 mL of glucose reference stock solution under Example 1, dilute to scale with purified water, and mix thoroughly. Accurately measure 10 mL of the above solution into an ultrafiltration centrifuge tube, centrifuge at 5000g for 90 min at 10°C, accurately measure 4 mL of the solution after centrifugation, place it in a 10 mL volumetric flask, dilute to scale with acetonitrile, and mix thoroughly. Prepare 3 copies in parallel.

[0057] Test sample spiked solution (100% concentration level): Accurately measure 5 mL of irinotecan hydrochloride liposome injection sample, place it in a 20 mL volumetric flask, accurately add 2.5 mL of glucose reference stock solution under Example 1, dilute to scale with purified water, and mix thoroughly. Accurately measure 10 mL of the above solution into an ultrafiltration centrifuge tube, centrifuge at 5000g for 90 min at 10°C, accurately measure 4 mL of the solution after centrifugation, place it in a 10 mL volumetric flask, dilute to scale with acetonitrile, and mix thoroughly. Prepare 3 copies in parallel.

[0058] Test sample spiked solution (80% concentration level): Accurately measure 5 mL of irinotecan hydrochloride liposome injection sample, place it in a 20 mL volumetric flask, accurately add 2 mL of glucose reference stock solution under Example 1, dilute to scale with purified water, and mix thoroughly. Accurately measure 10 mL of the above solution into an ultrafiltration centrifuge tube, centrifuge at 5000g for 90 min at 10°C, accurately measure 4 mL of the solution after centrifugation, place it in a 10 mL volumetric flask, dilute to scale with acetonitrile, and mix thoroughly. Prepare 3 copies in parallel.

[0059] Test sample spiked solution (20% concentration level): Accurately measure 2.5 mL of irinotecan hydrochloride liposome injection sample, place it in a 10 mL volumetric flask, accurately add 0.25 mL of glucose reference stock solution under Example 1, dilute to scale with purified water, and mix thoroughly. Transfer all of the above solution to an ultrafiltration centrifuge tube, centrifuge at 5000g for 90 minutes at 10°C, accurately measure 4 mL of the solution after centrifugation, place it in a 10 mL volumetric flask, dilute to scale with acetonitrile, and mix thoroughly. Prepare 3 copies in parallel.

[0060] The results were shown in Table 3.

[0061] Table 3 Accuracy

[0062] The above results show that the recoveries of glucose in the spiked solutions of the test sample at 120%, 100%, and 80% concentration levels are in the range of 90.0%~110.0%, and the recovery of glucose in the spiked solutions of the test sample at 20% concentration level is in the range of 80.0%~120.0%. The RSD values ​​of the recoveries at each concentration level are no more than 10.0%, indicating that the accuracy of this method is good.

[0063] 2.5 Solution stability The test solution prepared in Example 1 was placed at room temperature for 0 h, 6 h, 12 h, 24 h, and 48 h, and samples were taken for detection. The chromatograms were recorded. The results are shown in Table 4.

[0064] Table 4 Solution stability

[0065] The results showed that the absolute difference between the test results of glucose content in the test solution placed at different times and the test result at 0h did not exceed 2µg / mL, proving that the test solution had good stability.

[0066] 2.6 Linear range The reference solution 1 to the reference solution 5 under Example 1 and the quantitative limit solution under Example 2 were sampled and tested respectively, and the chromatograms were recorded. The results are shown in Table 5.

[0067] Table 5 Linear range

[0068] The test results showed that the linear relationship was good in the range of glucose concentration from the limit of quantification to 40µg / mL.

[0069] Comparative Example 1 This comparative example provides a method for detecting the residual glucose content in irinotecan hydrochloride liposome injection, which is different from that in Example 1 only in that the chromatographic column is a Waters-µBondapak® NH2 chromatographic column with a specification of 3.9 mm×300 mm and 10 µm, and the other detection conditions are exactly the same.

[0070] Take the sodium chloride reference solution and glucose reference solution under the specificity item of Example 2 for sampling and detection, and record the chromatogram, such as Figure 7~Figure 8 shown.

[0071] As can be seen from the figure, the peak time of sodium chloride is 7.627 min, and the peak time of glucose is 7.719 min. Glucose and the adjacent sodium chloride cannot be effectively separated, which does not meet the requirements for accurate quantitative detection of glucose.

[0072] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modification, equivalent substitution or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for detecting the residual glucose in irinotecan hydrochloride liposome injection, characterized in that: The detection is carried out by high performance liquid chromatography, including the following steps: (1) Preparation of test solution and mixed reference solution: Preparation of reference solution: Take glucose reference and prepare mixed reference solution with water; Preparation of test solution: Take a sample of irinotecan hydrochloride liposome injection and add water, mix well, ultrafilter, and centrifuge to obtain the test solution; (2) Take the reference solution and the test solution and perform the test according to the following liquid chromatography conditions: Column: Waters XBridge BEH HILIC, 250 mm × 4.6 mm, 5 µm; ELSD detector; Mobile phase: a mixed solution of acetate buffer and acetonitrile at pH 3.8-4.2, wherein the volume ratio of acetate buffer to acetonitrile is (88-92): (12-8); The elution mode was isocratic.

2. The method for detecting the residual glucose in irinotecan hydrochloride liposome injection according to claim 1, characterized in that: The volume ratio of acetate buffer to acetonitrile in the mobile phase is 90:

10.

3. The method for detecting the residual glucose in irinotecan hydrochloride liposome injection according to claim 2, characterized in that: The pH of the acetate buffer is 4.

0.

4. The method for detecting the residual glucose in irinotecan hydrochloride liposome injection according to claim 1, characterized in that: The column temperature is 38℃~42℃.

5. The method for detecting the residual glucose in irinotecan hydrochloride liposome injection according to claim 4, characterized in that: The column temperature was 40°C.

6. The method for detecting the residual glucose in irinotecan hydrochloride liposome injection according to claim 1, characterized in that: The flow rate is 0.8mL / min~1.2mL / min.

7. The method for detecting the residual glucose in irinotecan hydrochloride liposome injection according to claim 6, characterized in that: The flow rate was 1.0 mL / min.

8. The method for detecting the residual glucose in irinotecan hydrochloride liposome injection according to claim 1, characterized in that: The injection volume was 10 μL.

9. The method for detecting the residual glucose in irinotecan hydrochloride liposome injection according to claim 1, characterized in that: The preparation of the test solution specifically includes the following steps: taking a sample of irinotecan hydrochloride liposome injection, adding purified water in an amount of 1.8 to 2.2 times its volume, mixing evenly, ultrafiltration, and centrifugation to obtain a test solution.

10. The method for detecting the residual glucose in irinotecan hydrochloride liposome injection according to claim 9, characterized in that: The ultrafiltration membrane used in the ultrafiltration has a molecular weight cutoff of 9.5 KDa to 10.5 kDa; The centrifugal speed is 4500g~5500g, and the centrifugal time is 50min~90min.

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