A method for detecting the content of sodium octanoate in albumin-bound paclitaxel injection

Abstract

The present invention relates to a method for detecting the content of sodium octanoate in albumin-bound paclitaxel injection, and belongs to the technical field of quality control of albumin-bound paclitaxel injection. The present invention provides a method for detecting the content of sodium octanoate in albumin-bound paclitaxel injection, using high performance liquid chromatography, a chromatographic column with octadecylsilane bonded silica gel as a filler, and a mobile phase consisting of phase A and phase B, wherein mobile phase A is a mixed solution of phosphate buffer solution and acetonitrile, mobile phase B is acetonitrile, and mobile phases A and B are mixed in a certain proportion for gradient elution. The detection method provided by the present invention can quickly and accurately detect the content of sodium octanoate in albumin-bound paclitaxel injection, so as to determine whether the content of sodium octanoate in the imitation preparation is consistent with that of the reference preparation, and whether it meets the requirements of bioequivalence, and has practical promotion and application value.

Description

Technical Field

[0001] The invention relates to a method for detecting the content of sodium octanoate in an albumin-bound paclitaxel injection, and belongs to the technical field of quality control of albumin-bound paclitaxel injection. Background Art

[0002] Albumin-bound paclitaxel injection (trade name: ) is a new special targeted preparation of paclitaxel developed by Celgene, an American biopharmaceutical company. It is suitable for the treatment of metastatic breast cancer that has failed combined chemotherapy or breast cancer that has recurred within 6 months after adjuvant chemotherapy. It is a nanoparticle freeze-dried powder injection made of human albumin and paclitaxel through high-pressure vibration technology. The specification is that each bottle contains 100 mg of paclitaxel and about 900 mg of human albumin. Among them, sodium octanoate is used as an auxiliary material in the human albumin stabilizer. It can play a stabilizing and protective role in the heating and insulation process of human albumin, prevent the denaturation of albumin, and ensure that the product has a good appearance. However, sodium octanoate has a certain toxicity, and its content in human albumin needs to be controlled. According to the "Chinese Pharmacopoeia", the content of sodium octanoate in every 1g of protein should be 0.140~0.180mmol. If sodium octanoate is mixed with acetyltryptophan, the content of sodium octanoate in every 1g of protein should be 0.064~0.096mmol.

[0003] In addition, the European Medicines Agency (EMA) has announced special preparations The guiding principles of the drug administration clearly stipulate that the composition of the micelle infusion immediately before administration should be qualitatively and quantitatively the same as that currently approved, and satisfactory data should be provided to demonstrate similar physicochemical characteristics. Different from ordinary injections, special injections usually involve factors such as drug release and adsorption of body fluid components after entering the body. Therefore, the differences in the formulation and process of the test preparation and the reference preparation may lead to changes in the pharmacokinetic behavior of the drug in vivo, thereby bringing about changes in effectiveness and toxicity.

[0004] Based on the above considerations, we not only need to control the content of sodium octanoate in human serum albumin, but also need to study whether the content of sodium octanoate in the generic paclitaxel albumin preparation is consistent with the reference preparation.

[0005] At present, there are many literature reports on methods for detecting the content of sodium octanoate in human albumin, such as document 1 (Lu Shengjuan et al. Determination of sodium octanoate content in human albumin products by reversed-phase high performance liquid chromatography [J], Applied Technology, 2015, 4: 95-96.) using a Dion C18 chromatographic column, acetonitrile-water (40:60V / V) containing 0.05% trifluoroacetic acid isocratic elution, and the sample solution is prepared as follows: the human albumin preparation is diluted to 5% with pure water. Then, twice the acetonitrile solution containing 0.05% trifluoroacetic acid is added to the 5% solution, mixed, and centrifuged. The inventor tried to precipitate paclitaxel (albumin-bound) preparation with acetonitrile solution, and found that albumin nanoparticles would agglomerate to form a block precipitate, and sodium octanoate would be wrapped therein, resulting in sodium octanoate not being accurately quantified.

[0006] Document 2 (Part IV of the 2020 edition of the Pharmacopoeia of the People's Republic of China) uses gas chromatography to detect the content of sodium octanoate in human serum albumin. The inventors use the pharmacopoeia method to detect the content of sodium octanoate in paclitaxel (albumin-bound) preparations, but find that the sample pretreatment process is cumbersome, and the chloroform extraction solvent needs to be evaporated to dryness first, and then the volatiles need to be dissolved with an appropriate amount of chloroform before sampling; in addition, human serum albumin and sodium octanoate are separated by centrifugation. Since the aqueous phase and the chloroform organic phase are not easy to be completely separated, a small amount of albumin will be present in the volatiles, and dissolving it with an appropriate amount of chloroform will form a black residue, which interferes with the sampling detection.

[0007] Therefore, the existing technology cannot detect the content of sodium octanoate in paclitaxel for injection (albumin-bound), and a method for quickly and accurately detecting the content of sodium octanoate in the preparation is urgently needed. Summary of the invention

[0008] The present invention aims to provide a method for rapidly and accurately detecting the content of sodium octanoate in paclitaxel for injection (albumin-bound type).

[0009] To achieve the above object, the present invention provides a method for detecting the content of sodium octanoate in paclitaxel for injection (albumin-bound) by high performance liquid chromatography, wherein the high performance liquid chromatography adopts a chromatographic column with octadecylsilane bonded silica gel as a filler, and performs gradient elution with mobile phases A and B in a certain proportion; wherein the mobile phase A is a mixed solution of phosphate buffer solution and acetonitrile; the mobile phase B is acetonitrile;

[0010] Furthermore, the chromatographic column of the present invention is a YMC-Pack ODS-A having a specification of 4.6 mm×150 mm×3 μm or a chromatographic column of equivalent performance;

[0011] Furthermore, the mobile phase A phosphate buffer solution of the present invention is selected from one or more of sodium dihydrogen phosphate, disodium hydrogen phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium phosphate, sodium phosphate, ammonium dihydrogen phosphate, diammonium hydrogen phosphate, and ammonium phosphate buffer;

[0012] Preferably, the mobile phase A phosphate buffer solution is sodium dihydrogen phosphate;

[0013] Furthermore, a pH regulator is added to the mobile phase A, and the addition of a pH regulator to the mobile phase helps to separate substances and improve peak shape, thereby making the accuracy and precision of the detection results higher;

[0014] Preferably, the pH adjuster is an acid;

[0015] More preferably, the pH adjuster is phosphoric acid;

[0016] Furthermore, the mobile phase A of the present invention is a mixed solution of sodium dihydrogen phosphate solution and acetonitrile, and the pH value of the sodium dihydrogen phosphate solution is adjusted to 2.7-2.9 with phosphoric acid; the volume ratio of the sodium dihydrogen phosphate solution to acetonitrile in the mixed solution is 50:50;

[0017] Furthermore, the mobile phase A of the present invention is a sodium dihydrogen phosphate solution with a concentration of 0.03 mol / L;

[0018] Furthermore, the mobile phases A and B described in the present invention are mixed in a certain ratio for gradient elution, and the gradient ratio is:

[0019] 0→15min, the volume ratio of mobile phase A to B is 100:0,

[0020] 20min, the volume ratio of mobile phase A to B is 50:50,

[0021] 20.1→30min, the volume ratio of mobile phase A to B was 100:0;

[0022] Further, the chromatographic condition flow rate of the present invention is 0.8 to 1.2 mL / min;

[0023] Preferably, the flow rate is 1 mL / min;

[0024] Furthermore, the chromatographic conditions of the present invention have an injection volume of 10 to 20 μl;

[0025] Preferably, the injection volume is 20 μl;

[0026] Furthermore, the chromatographic condition column temperature of the present invention is 20-50°C;

[0027] Preferably, the column temperature is 25°C;

[0028] Furthermore, the chromatographic condition detector described in the present invention is an ultraviolet detector;

[0029] Furthermore, the chromatographic conditions of the present invention have a detection wavelength of 210±5 nm;

[0030] Preferably, the detection wavelength is 210 nm;

[0031] The present invention also provides a method for detecting the content of sodium octanoate in paclitaxel for injection (albumin-bound) by high performance liquid chromatography, comprising the following steps:

[0032] (1) Test solution: Take 1 bottle of paclitaxel (albumin-bound) preparation, add 20 ml of 0.9% sodium chloride solution, shake gently to disperse, accurately measure 3 ml, place in a 10 ml volumetric flask, dilute to scale with methanol, vortex for 2 min, filter, accurately measure 4 ml of the filtrate, place in a 10 ml volumetric flask, dilute to scale with mobile phase A, and shake well;

[0033] (2) Reference solution: Take an appropriate amount of sodium octanoate, weigh it accurately, dissolve it in mobile phase A and quantitatively dilute it to make a solution containing about 86.4 μg per 1 ml;

[0034] (3) Subject the test solution and the reference solution to liquid chromatography, record the chromatograms, and analyze the results using the external standard method.

[0035] Beneficial effects of the present invention:

[0036] The present invention provides a method for detecting the content of sodium octanoate in paclitaxel for injection (albumin-bound) by high performance liquid chromatography, which has the advantages of high accuracy, high sensitivity, good repeatability and good specificity. The detection method provided by the present invention can quickly and accurately detect the content of sodium octanoate in paclitaxel for injection (albumin-bound), so as to judge whether the content of sodium octanoate in the imitation paclitaxel for injection (albumin-bound) preparation is consistent with the reference preparation and whether it meets the requirements of bioequivalence, and has practical promotion and application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 is the HPLC detection chromatogram of the blank solution in Example 1 of the present invention;

[0038] Figure 2 is a HPLC detection chromatogram of the impurity-spiked test solution in Example 1 of the present invention;

[0039] Figure 3It is the HPLC detection chromatogram of the test solution in Example 1 of the present invention. DETAILED DESCRIPTION

[0040] The present invention provides a method for rapidly and accurately detecting the content of sodium octanoate in paclitaxel for injection (albumin-bound). Those skilled in the art can refer to the content of this article and appropriately improve the chromatographic condition parameters to achieve the above. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included within the scope of the present invention. The method and application of the present invention have been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the method and application of this article without departing from the content, spirit and scope of the present invention to implement and apply the technology of the present invention.

[0041] The raw materials and equipment used in the specific embodiments of the present invention are all known products, which are purchased from the market, except for the reference preparation paclitaxel for injection (albumin-bound), which is purchased from Celgene Europe BV with a specification of 100 mg / bottle; the generic paclitaxel for injection (albumin-bound) preparation is obtained by Sichuan Huiyu Pharmaceutical Co., Ltd., and its preparation process is to treat paclitaxel and medicinal human serum albumin through shear emulsification, homogenization, evaporation, and sterilization filtration to obtain a sterile lyophilized product.

[0042] In the present invention, the abbreviations involved have the following meanings:

[0043] Impurity A: Cephalomannine; Impurity B: 7-epipaclitaxel; Impurity C: Baccatin III; Impurity D: (2R, 3S)-N-benzoyl-3-phenylisoserine methyl ester; Impurity E: (2R, 3S)-N-benzoyl-3-phenylisoserine ethyl ester; Impurity F: 10-deacetylpaclitaxel; Impurity G: 7-epi-10-deacetylpaclitaxel; Impurity H: 7-epiphalomannine; Impurity I: Paclitaxel C; Impurity J: N-methylpaclitaxel C; Impurity K: C3-C11 bridge paclitaxel isomer.

[0044] Paclitaxel for injection (albumin-bound) is also called albumin-bound paclitaxel injection.

[0045] Example 1

[0046] 1.1 Chromatographic conditions

[0047] Mobile phase A: a mixed solution of 0.03 mol / L sodium dihydrogen phosphate (pH adjusted to 2.8 ± 0.1 with phosphoric acid) and acetonitrile in a volume ratio of 50:50;

[0048] Mobile phase B: acetonitrile;

[0049] Elution mode: gradient elution, as follows: 0→15min, the volume ratio of mobile phase A to B is 100:0; 20min, the volume ratio of mobile phase A to B is 50:50; 20.1→30min, the volume ratio of mobile phase A to B is 100:0;

[0050] Column temperature: 25°C;

[0051] Injection volume: 20 μl;

[0052] Flow rate: 1ml / min;

[0053] Detection wavelength: 210nm;

[0054] Running time: 30min.

[0055] Blank solution / diluent: Prepare the same as “mobile phase A”.

[0056] Reference solution: Take an appropriate amount of sodium octanoate, dissolve it in a diluent and quantitatively dilute it to make a solution containing approximately 86.4 μg per 1 ml.

[0057] Impurity mixed solution: Weigh appropriate amount of impurities A, B, C, D, E, F, G, H, I, J, and K respectively, place in a 25 ml volumetric flask, add diluent to dissolve and dilute to the scale, and shake well.

[0058] Test sample stock solution: Take 1 bottle of paclitaxel (albumin-bound) preparation, add 20 ml of 0.9% sodium chloride solution, and shake gently to disperse.

[0059] Test solution: Measure 3 ml of the test sample stock solution, place it in a 10 ml volumetric flask, dilute it to the mark with methanol, vortex for 2 minutes, filter, accurately measure 4 ml of the filtrate, place it in a 10 ml volumetric flask, dilute it to the mark with diluent, and shake well.

[0060] Impurity spiked test solution: Measure 3 ml of the test sample stock solution, place it in a 10 ml volumetric flask, dilute it to the scale with methanol, vortex for 2 minutes, filter, accurately measure 4 ml of the filtrate, place it in a 10 ml volumetric flask, add 200 μl of the impurity mixed solution, dilute it to the scale with diluent, and shake well.

[0061] 1.2 Exclusivity

[0062] Test method: Accurately measure 20 μL of the blank solution, impurity spiked test solution, reference solution and test solution respectively and inject them into the liquid chromatograph, record the chromatogram, and calculate the content of sodium octanoate in paclitaxel (albumin-bound) preparation by peak area according to the external standard method. The formula is:

[0063] Content (mmol / g protein) = (A 供 ×C 对×V) / (A 对 ×167.2×M)

[0064] Where: A 供 is the peak area of ​​the test solution;

[0065] A 对 is the peak area of ​​the reference solution;

[0066] C 对 is the concentration of the reference solution, mg / ml;

[0067] V is the dilution factor of the test solution;

[0068] 167.2: Molecular weight of sodium octanoate;

[0069] M: albumin content, g / bottle.

[0070] Test results: Blank solution does not interfere with the peak of sodium octanoate ( Figure 1 The known impurities A, B, C, D, E, F, G, H, I, J, and K in the impurity spiked test solution did not interfere with the peak of sodium octanoate, and the separation degrees of sodium octanoate and the adjacent peaks were 1.9 and 4.4 ( Figure 2 The separations of sodium octanoate and adjacent peaks in the test solution were 6.0 and 4.3 ( Figure 3 ),Depend on Figures 1 to 3 It can be seen that the detection method of the present invention has good specificity. Among them, the peak area of ​​sodium octanoate in the test solution is 24.511, and the content of sodium octanoate in the test solution calculated by the peak area according to the above external standard method is 0.0873 (mmol / g albumin). At the same time, the content of sodium octanoate in the reference preparation calculated according to the chromatographic conditions and the external standard method is 0.0876 (mmol / g albumin), indicating that the content of sodium octanoate in our imitation paclitaxel (albumin-bound) preparation is basically consistent with the reference preparation.

[0071] 1.3 Limit of quantification and limit of detection

[0072] Test method: Accurately weigh 22.33 mg of sodium octanoate reference substance, place it in a 50 ml volumetric flask, add diluent (mobile phase A) to dissolve and dilute to the scale, shake well; dilute step by step, so that the peak height of sodium octanoate is 10 to 20 times the baseline noise, which is the quantitative limit, and this is used as the quantitative limit solution; the peak height of sodium octanoate is 3 to 10 times the baseline noise, which is the detection limit, and this is used as the detection limit solution.

[0073] The quantitative limit and detection limit solutions were tested according to the above chromatographic conditions and the chromatograms were recorded. The results are shown in Table 1 below:

[0074] Table 1 Results of quantitative limit and detection limit of sodium caprylate

[0075] name Limit of quantitation (ug / ml) Limit of quantification (%) Detection limit (ug / ml) Detection limit (%) Sodium Caprylate 1.1053 1.47 0.3316 0.44％

[0076] The results in Table 1 show that the sensitivity of the detection method of the present invention meets the detection requirements.

[0077] 1.4 Linearity

[0078] Test method: Weigh 21.613 mg of sodium octanoate reference substance accurately, place in a 50 ml volumetric flask, add diluent to dissolve and dilute to scale, shake well. This solution is the reference substance stock solution.

[0079] Reference substance solution: Accurately measure 5 ml of reference substance stock solution, place in a 25 ml volumetric flask, dilute to the mark with diluent, and shake well.

[0080] Quantitation limit solution: Accurately measure 1.25 ml of the reference solution, place it in a 100 ml volumetric flask, dilute to the mark with diluent, and shake well.

[0081] 40% linear solution: Accurately measure 2 ml of the reference stock solution, place it in a 25 ml volumetric flask, add diluent to dilute to the scale, and shake well.

[0082] 80% linear solution: Accurately measure 4 ml of the reference stock solution, place it in a 25 ml volumetric flask, add diluent to dilute to the scale, and shake well.

[0083] 100% linear solution: same as reference solution.

[0084] 150% linear solution: Accurately measure 3 ml of the reference stock solution, place it in a 10 ml volumetric flask, add diluent to dilute to the scale, and shake well.

[0085] 250% linear solution: Accurately measure 5 ml of the reference stock solution, place it in a 10 ml volumetric flask, add diluent to dilute to the scale, and shake well.

[0086] The quantitative limit solution, 40%, 100%, 150%, and 250% linear solutions were tested according to the above detection method and chromatographic conditions, and the chromatograms were recorded. A linear regression was performed on the peak area Y with the concentration X (mg / ml), and the regression equation and correlation coefficient were calculated. The results are shown in Table 2 below:

[0087] Table 2 Sodium octanoate linear results

[0088]

[0089]

[0090] The results in Table 2 show that within the range of 1.0698 μg / ml to 213.9687 μg / ml, the peak area of ​​sodium octanoate has a good linear relationship with the measured concentration, wherein the correlation coefficient R is 0.9999.

[0091] 1.5 Accuracy

[0092] Test method: Accurately weigh 45.60 mg of sodium octanoate reference substance, place it in a 20 ml volumetric flask, add diluent to dissolve and dilute to the scale, shake well, and use it as the reference substance stock solution.

[0093] Test sample stock solution: Take 2 bottles of paclitaxel (albumin-bound) preparation, add 20 ml of 0.9% sodium chloride solution to each bottle, shake gently to disperse evenly, and mix into one bottle.

[0094] Unspiked solution: Accurately measure 3 ml of the test sample stock solution, place it in a 10 ml volumetric flask, dilute to the scale with methanol, and shake well.

[0095] 20%, 100%, 150% recovery rate solution: accurately measure 3ml of the test sample stock solution, place it in a 10ml volumetric flask, accurately add 0.2ml, 1ml, and 1.5ml of the reference sample stock solution, dilute to the scale with methanol, vortex for 2min, filter, accurately measure 4ml of the filtrate, place it in a 10ml volumetric flask, dilute to the scale with the diluent, and shake well. Prepare 3 portions of 20%, 100%, and 150% recovery rate solutions in parallel, for a total of 9 portions. Accurately measure 20μl of each sample and record the chromatogram. The results are shown in Table 3 below:

[0096] Table 3 Sodium Caprylate Recovery Results

[0097]

[0098]

[0099] The results in Table 3 show that the recovery rate of sodium octanoate in paclitaxel (albumin-bound) preparations is between 95% and 105%, and the RSD is 1.86%, indicating that the detection method of the present invention has good accuracy.

[0100] 1.6 Repeatability and precision

[0101] Test method: Precisely measure 3 ml of the stock solution of the test sample with "2.3 accuracy", place it in a 10 ml volumetric flask, dilute it to the mark with methanol, vortex for 2 minutes, filter, accurately measure 4 ml of the filtrate, place it in a 10 ml volumetric flask, dilute it to the mark with the diluent, and shake well. Prepare 12 portions in parallel, of which 6 portions are used as repeatability solutions and the other 6 portions are used as intermediate precision solutions.

[0102] Accurately measure 20 μl of the repeatability solution, intermediate precision solution and "1.4 linearity" prepared reference solution, respectively, and perform the tests according to the above test method and chromatographic conditions, and record the chromatograms. The results are shown in Tables 4 to 6 below:

[0103] Table 4 Sodium octanoate repeatability results

[0104]

[0105] Table 5 Intermediate precision results of sodium octanoate

[0106]

[0107] Table 6 Sodium octanoate precision results

[0108]

[0109] The results in Table 6 show that the detection method of the present invention has good precision.

[0110] Comparative Example 1

[0111] Test method: The sample solution preparation method of reference 1 uses acetonitrile as a precipitant to precipitate albumin in paclitaxel (albumin-bound) preparations. The specific sample preparation is as follows:

[0112] Unspecified test sample solution: Accurately measure 3 ml of the "1.5 accuracy" test sample stock solution, place it in a 10 ml volumetric flask, dilute to the scale with acetonitrile, vortex for 2 minutes, filter, take 4 ml of the filtrate, place it in a 10 ml volumetric flask, dilute to the scale with diluent, shake well, and obtain.

[0113] Spiked 100% test sample solution: accurately measure 3 ml of "1.5 accuracy" test sample stock solution, place in a 10 ml volumetric flask, accurately add 1 ml of sample stock solution, dilute to the scale with acetonitrile, vortex for 2 minutes, filter, take 4 ml of the filtrate, place in a 10 ml volumetric flask, dilute to the scale with diluent, and shake well.

[0114] Spiked 120% test solution: accurately measure 3 ml of "1.5 accuracy" test sample stock solution, place in a 10 ml volumetric flask, accurately add 1.2 ml of reference sample stock solution, dilute to scale with acetonitrile, vortex for 2 minutes, filter, take 2 ml of the filtrate, place in a 10 ml volumetric flask, dilute to scale with diluent, and shake well.

[0115] Each accurately measured 20 μl of sample and recorded the chromatogram. The results are shown in Table 7 below:

[0116] Table 7 Sodium Caprylate Recovery Results

[0117]

[0118] The results in Table 7 show that the recovery rates of sodium octanoate in the test solutions spiked with 100% and 120% do not meet the recovery rate requirements specified in the Chinese Pharmacopoeia (the recovery rate range is specified according to the limit of the detection target. Since the limit of sodium octanoate is 14.4 mg / bottle, its recovery rate limit should be 95% to 105%), indicating that when acetonitrile is used as a precipitant, albumin nanoparticles will agglomerate to form a block-like precipitate, and sodium octanoate will be wrapped therein, resulting in the inability to accurately quantify sodium octanoate.

[0119] 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 content of sodium caprylate in albumin-bound paclitaxel injection, characterized in that: High performance liquid chromatography was used, the chromatographic column was filled with octadecylsilane bonded silica gel, the mobile phase was composed of phase A and phase B, wherein mobile phase A was a mixed solution of phosphate buffer solution and acetonitrile, and mobile phase B was acetonitrile; The specifications of the chromatographic column are 4.6mm×150mm×3μm; The concentration of the sodium dihydrogen phosphate solution in the mobile phase A is 0.03 mol / L, and the pH value is 2.7-2.9; the volume ratio of the sodium dihydrogen phosphate solution to acetonitrile in the mobile phase A is 50:50; The detection method uses mobile phases A and B for gradient elution in a certain ratio, and the gradient elution ratio is: 0-15min, 100% A; 20min, 50% A; 20.1-30min, 100% A; The test solution is: take 1 bottle of albumin-bound paclitaxel preparation, add 20 ml of 0.9% sodium chloride solution, shake gently to disperse, accurately measure 3 ml, place in a 10 ml volumetric bottle, dilute to the scale with methanol, vortex for 2 minutes, filter, accurately measure 4 ml of the filtrate, place in a 10 ml volumetric bottle, dilute to the scale with solvent, and shake well.

2. The detection method according to claim 1, characterized in that: The chromatographic column is YMC-Pack ODS-A.

3. The detection method according to claim 1, characterized in that: The phosphate buffer solution in the mobile phase A is selected from one or more of sodium dihydrogen phosphate, disodium hydrogen phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium phosphate, sodium phosphate, ammonium dihydrogen phosphate, diammonium hydrogen phosphate, and ammonium phosphate buffer.

4. The detection method according to claim 3, characterized in that: Phosphate buffer solution is sodium dihydrogen phosphate solution.

5. The detection method according to claim 1, characterized in that: The flow rate of the mobile phase is 0.8~1.2mL / min.

6. The detection method according to claim 5, characterized in that: The mobile phase flow rate was 1 mL / min.

7. The detection method according to claim 1, characterized in that: The column temperature is 20-50°C.

8. The detection method according to claim 7, characterized in that: The column temperature was 25°C.

9. The detection method according to claim 1, characterized in that: The detection was carried out using an ultraviolet detector with a detection wavelength of 210±5nm.

10. The detection method according to claim 9, characterized in that: Detection wavelength: 210nm.

11. A method for detecting the content of sodium caprylate in albumin-bound paclitaxel injection, characterized in that: The following steps are involved: (1) Test solution: Take 1 bottle of albumin-bound paclitaxel preparation, add 20 ml of 0.9% sodium chloride solution, shake gently to disperse, accurately measure 3 ml, place in a 10 ml volumetric flask, dilute to the mark with precipitant, vortex for 2 min, filter, accurately measure 4 ml of the filtrate, place in a 10 ml volumetric flask, dilute to the mark with solvent, and shake well; (2) Reference solution: Take an appropriate amount of sodium octanoate, weigh it accurately, dissolve it in a solvent and quantitatively dilute it to make a solution containing about 86.4 μg per 1 ml; (3) Determine the test solution and the reference solution according to the detection method, record the chromatogram, and analyze the measurement results according to the external standard method; The detection method adopts high performance liquid chromatography, the chromatographic column uses octadecylsilane bonded silica gel as a filler, the mobile phase consists of phase A and phase B, wherein mobile phase A is a mixed solution of phosphate buffer solution and acetonitrile, and mobile phase B is acetonitrile; The specifications of the chromatographic column are 4.6mm×150mm×3μm; The concentration of the sodium dihydrogen phosphate solution in the mobile phase A is 0.03 mol / L, and the pH value is 2.7-2.9; the volume ratio of the sodium dihydrogen phosphate solution to acetonitrile in the mobile phase A is 50:50; The detection method uses mobile phases A and B for gradient elution in a certain ratio, and the gradient elution ratio is: 0-15min, 100% A; 20min, 50% A; 20.1-30min, 100% A; Wherein, the precipitant is methanol, and the solvent is mobile phase A.

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