Method for determining the content of concentrated oral solution of magnesium sulfate, sodium and potassium

Abstract

This invention discloses a method for determining the content of magnesium sulfate sodium potassium oral concentrate. The method includes taking a sample of the magnesium sulfate sodium potassium oral concentrate, diluting it with an ammonium chloride solution containing approximately 0.18 mmol / L ammonium ions as a solvent, performing ion chromatography with specific chromatographic parameters, and calculating the content of magnesium sulfate, sodium sulfate, and potassium sulfate in the solution using the external standard method. This invention is simple to operate, time-saving, labor-saving, easy to master, highly specific, accurate, and precise, providing accurate results. It can be used for the determination of the content of magnesium sulfate sodium potassium oral concentrate.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical analysis technology. Specifically, it relates to a method for determining the content of magnesium sulfate, sodium sulfate, and potassium sulfate in a concentrated oral solution of magnesium sulfate sodium potassium sulfate for quality control, as well as a method for determining the content of magnesium sulfate, sodium sulfate, and potassium sulfate in any combination. Background Technology

[0002] Magnesium sodium potassium sulfate oral concentrated solution was developed by Braintree Laboratories in the United States and approved by the FDA in August 2010. Its brand name is [Brand Name Missing]. The Bowel Prep Kit comes in 6-ounce (approximately 177 ml) bottles and contains 1.6 g magnesium sulfate, 17.5 g sodium sulfate, and 3.13 g potassium sulfate. This product is a laxative suitable for bowel preparation in adult patients prior to colonoscopy. The original product was approved for marketing in China in November 2022, with registration number HJ20220094.

[0003] Currently, the concentrated oral solution of sodium potassium magnesium sulfate is not included in the pharmacopoeia standards at home and abroad. Therefore, based on the characteristics of the product, a method for determining the cations in the solution has been developed to determine the content of the three active ingredients in the concentrated oral solution of sodium potassium magnesium sulfate. Summary of the Invention

[0004] In view of the formulation and manufacturing process characteristics of concentrated oral magnesium sodium potassium sulfate solution, and to ensure effective quality control in the research and development and production of concentrated oral magnesium sodium potassium sulfate solution, the purpose of this invention is to provide a method for determining the content of magnesium sulfate, sodium sulfate, and potassium sulfate in a solution using ion chromatography, through extensive experimental research. This detection method can be used for the content determination of concentrated oral magnesium sodium potassium sulfate solution, and is accurate, reliable, highly specific, time-saving, labor-saving, and easy to operate.

[0005] In order to achieve the purpose of this invention, the inventors conducted extensive experiments and research and made unremitting efforts, and finally obtained the following technical solution:

[0006] A method for determining the content of a concentrated oral solution of sodium potassium magnesium sulfate involves taking the concentrated oral solution of sodium potassium magnesium sulfate and determining the content of each component using the following chromatographic method.

[0007] The sample was determined by ion chromatography (General Chapter 0513, 2020 edition of the Chinese Pharmacopoeia).

[0008] Weigh approximately 20 mg of ammonium chloride and dissolve it in 2000 ml of ultrapure water to obtain the blank solvent.

[0009] Accurately measure 1.0 ml of this product into a 50 ml volumetric flask, dilute to the mark with blank solvent, and shake well. Then accurately measure 2.0 ml into a 50 ml volumetric flask, dilute to the mark with blank solvent, and shake well to obtain the test solution.

[0010] To prepare the reference solution, take appropriate amounts of magnesium, sodium, and potassium single-element standard solutions, and quantitatively dilute them with blank solvent to prepare a solution containing 1.4 μg of magnesium, 25.6 μg of sodium, and 6.4 μg of potassium per ml. Shake well to obtain the solution.

[0011] Chromatographic conditions: Cation exchange column (Dionex IonPac™ CS12A IC™ Analytical, 250 mm × 4 μm; Dionex IonPac™ CG12A IC, 50 × 5 mm or equivalent column); 20 mmol / L methanesulfonic acid solution as eluent; column temperature 32℃; flow rate 0.7 ml / min; injection volume 100 μl; run time 30 min.

[0012] The system suitability requirements are that the elution order of the reference solution chromatogram should be sodium, ammonium, potassium, and magnesium; the resolution of the sodium, ammonium, potassium, and magnesium ion peaks with adjacent ion peaks should meet the requirements, and the theoretical plate number calculated based on the sodium and potassium ion peaks should not be less than 2000.

[0013] For the assay, accurately measure the test solution and reference solution, inject them separately into the ion chromatograph, and record the chromatograms. Calculate the result based on the peak area using the external standard method.

[0014] Compared with existing technologies, the method for determining the content of magnesium sulfate sodium potassium oral concentrated solution of the present invention has the following advantages and significant progress: it is highly specific, accurate, easy to master, and precise. It can be used for determining the content of magnesium sulfate, sodium sulfate, and potassium sulfate in magnesium sulfate sodium potassium oral concentrated solution, as well as for determining the content of magnesium sulfate, sodium sulfate, and potassium sulfate in any combination. Attached Figure Description

[0015] Figure 1 Graph of reference solution for the determination of the content of sodium potassium magnesium sulfate oral concentrate;

[0016] Figure 2 Typical chromatogram of the test solution for the determination of the content of sodium potassium magnesium sulfate in oral concentrated solution. Detailed Implementation

[0017] The following examples provide a more detailed description of the method for determining the content of sodium potassium magnesium sulfate oral concentrated solution involved in this invention. However, this should not be construed as limiting the scope of the above-mentioned subject matter of this invention to the following examples. All technologies implemented based on the above-mentioned content of this invention fall within the scope of this invention.

[0018] Example 1: Precision Study of the Measurement Method of the Present Invention

[0019] (1) Precision

[0020] Take an appropriate amount of this product and determine the contents of magnesium sulfate, sodium sulfate, and potassium sulfate according to the proposed content method. Repeat the determination 6 times to examine the precision of the method. The results are shown in Table 1 below.

[0021] Table 1 Precision results of the test solution

[0022]

[0023] Experimental results show that when the measurements were repeated 6 times, the RSD of the measurement deviation was less than 1%, indicating that the method has good precision.

[0024] Example 2: Accuracy Study of the Measurement Method of the Present Invention

[0025] (2) Recovery rate

[0026] Take appropriate amounts of magnesium sulfate, sodium sulfate, and potassium sulfate, and prepare a simulated formulation solution using a blank excipient solution at a ratio of 80% to 120% of the formulation composition. Determine the content of magnesium sulfate, sodium sulfate, and potassium sulfate in the simulated formulation solution according to the proposed content method, and calculate the recovery rate of each component. The results are shown in Table 2 below.

[0027] Table 2 Recovery rate test of the test sample solution

[0028]

[0029] As shown in the table above, the recovery rates at each level were between 98% and 102%, indicating good recovery rates and high accuracy of the method.

[0030] Example 3: Linearity Study of the Measurement Method of the Present Invention

[0031] (3) Linear

[0032] Take appropriate amounts of standard solutions of magnesium, sodium, and potassium, respectively, and dilute them with blank solvent to prepare gradient concentration solutions. Accurately measure 100 μl of each solution and inject it into an ion chromatograph. Record the chromatograms. Plot standard curves for each component with peak area A as the ordinate and corresponding concentration C as the abscissa, and calculate the regression equations. The results are shown in Table 3.

[0033] Table 3 Linear Regression

[0034]

[0035] Example 4: Sample determination test of the method of the present invention

[0036] (4) Sample determination

[0037] The sample was determined by ion chromatography (General Chapter 0513, 2020 edition of the Chinese Pharmacopoeia).

[0038] Weigh approximately 20 mg of ammonium chloride and dissolve it in 2000 ml of ultrapure water to obtain the blank solvent.

[0039] Accurately measure 1.0 ml of this product into a 50 ml volumetric flask, dilute to the mark with blank solvent, and shake well. Then accurately measure 2.0 ml into a 50 ml volumetric flask, dilute to the mark with blank solvent, and shake well to obtain the test solution.

[0040] To prepare the reference solution, take appropriate amounts of magnesium, sodium, and potassium single-element standard solutions, and quantitatively dilute them with blank solvent to prepare a solution containing 1.4 μg of magnesium, 25.6 μg of sodium, and 6.4 μg of potassium per ml. Shake well to obtain the solution.

[0041] Chromatographic conditions: Cation exchange column (Dionex IonPac™ CS12A IC™ Analytical, 250 mm × 4 μm; Dionex IonPac™ CG12A IC, 50 × 5 mm or equivalent column); 20 mmol / L methanesulfonic acid solution as eluent; column temperature 32℃; flow rate 0.7 ml / min; injection volume 100 μl; run time 30 min.

[0042] The system suitability requirements are that the elution order of the reference solution chromatogram should be sodium, ammonium, potassium, and magnesium; the resolution of the sodium, ammonium, potassium, and magnesium ion peaks with adjacent ion peaks should meet the requirements, and the theoretical plate number calculated based on the sodium and potassium ion peaks should not be less than 2000.

[0043] For the assay, accurately measure the test solution and reference solution, inject them separately into the ion chromatograph, and record the chromatograms. Calculate the result based on the peak area using the external standard method.

[0044] The results are shown in Table 4.

[0045] Table 4. Results of content determination of concentrated oral magnesium sulfate sodium potassium solution

[0046] Inspection items 33230501 33230601 33230602 magnesium sulfate content 99.6％ 98.1％ 96.9％ Sodium sulfate content 99.4％ 99.3％ 98.6％ Potassium sulfate content 99.4％ 99.4％ 99.2％

[0047] Methodological studies have shown that the content determination method of this invention has good specificity, accuracy, and precision, and is suitable for the determination of the content of magnesium sulfate, sodium sulfate, and potassium sulfate in concentrated oral magnesium sulfate sodium potassium solution.

[0048] Table 5 Summary of the methodological validation of the content determination of the present invention

[0049]

Claims

1. A method for determining the content of a concentrated oral solution of sodium magnesium sulfate and potassium sulfate, comprising sodium sulfate, potassium sulfate, and magnesium sulfate, characterized in that, Includes the following steps: (1) Determined by ion chromatography, using a cation exchange column and a conductivity detector; detection method is conductivity suppression detection, column temperature 25-35℃, with methanesulfonic acid solution as the eluent and flow rate 0.5-0.8 ml / min.

2. The analytical method for the content of sodium sulfate, potassium sulfate, and magnesium sulfate mixed solution as described in claim 1, characterized in that, Includes the following steps: (1) Use a cation exchange column, IonPac column TM The CS12A is a suitable, or equally effective, chromatographic column. Column temperature: 25-35℃. (2) Use methanesulfonic acid solution as the eluent with a concentration of 0.01mol / L-0.05mol / L and a flow rate of 0.5-0.8ml / min. (3) Use ammonium ion solution as a diluent to dilute the solution to a suitable concentration.

3. The analytical method for the content of sodium sulfate, potassium sulfate, and magnesium sulfate mixed solution according to claim 2, characterized in that, In step (1), the column temperature is 30℃.

4. The analytical method for the content of sodium sulfate, potassium sulfate, and magnesium sulfate mixed solution according to claim 2, characterized in that, In step (2), methanesulfonic acid solution was used as the eluent with a concentration of 0.02 mol / L and a flow rate of 0.7 ml / min.

5. The method for analyzing the content of sodium sulfate, potassium sulfate, and magnesium sulfate mixed solution according to claim 2, characterized in that, In step (3), ammonium ion solution is used as the diluent. Ammonium chloride is prepared into a solution containing about 0.18 mmol / L of ammonium ions using ultrapure water.

6. The analytical method for the content of sodium sulfate, potassium sulfate, and magnesium sulfate mixed solution according to claim 1, characterized in that, In step (3), the concentration of sodium ions in the test solution is 0-1.2 mmol / L, the concentration of potassium ions is 0-0.2 mmol / L, the concentration of magnesium ions is 0-0.1 mmol / L, and the diluent is ammonium chloride solution.

7. The analytical method for the content of sodium sulfate, potassium sulfate, and magnesium sulfate mixed solution according to claim 1, characterized in that, Includes the following steps: Weigh an appropriate amount of ammonium chloride and dissolve it in ultrapure water to prepare a solution containing approximately 0.18 mmol / L of ammonium ions. Take an appropriate amount of the test sample and dilute it with a diluent to prepare a solution of suitable concentration. Prepare reference solutions by quantitatively diluting appropriate amounts of sodium, potassium, and magnesium single-element standard solutions with blank solvent to the corresponding concentrations. (Sodium: 1.1 mmol / L, Potassium: 0.16 mmol / L, Magnesium ion concentration: 0.06 mmol / L) Chromatographic conditions: A cation exchange column (Dionex IonPac™ CS12A IC™ Analytical, 250 mm × 4 μm; Dionex IonPac™ CG12A IC, 50 × 5 mm or equivalent column) was used; a conductivity detector was used; the detection method was suppressed conductivity detection; the column temperature was 30 °C; 0.02 mol / L methanesulfonic acid solution was used as the eluent; and the flow rate was 0.7 ml / min. The system suitability requirements are that the elution order of the reference solution chromatogram is sodium, ammonium, potassium, and magnesium; the resolution between the sodium, ammonium, potassium, and magnesium ion peaks and adjacent ion peaks is not less than 1.5, and the theoretical plate number calculated based on the sodium and potassium ion peaks is not less than 2000.

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