An ion chromatography method for detecting the content of sodium, potassium, calcium and magnesium ions in injection

Abstract

The present invention discloses an ion chromatography method for detecting the content of sodium, potassium, calcium and magnesium ions in an injection. The method adopts a cation exchange chromatography column Dionex IonPac CS12A RFIC Analytical 4mm×250mm and a guard column Dionex IonPac CG12A RFIC Guard 4mm×50mm; a 20mmol / L methanesulfonic acid solution is used as the mobile phase, isocratic elution is performed, the detector is a conductivity detector, the detection method is suppressed conductivity detection, the column temperature is 25-40°C, the flow rate is 0.5-3ml / min, and the injection volume is 10-50μl. The method of the present invention is easy to operate, greatly improves the detection efficiency, and the method has strong specificity, good separation, high precision and accuracy, and good durability.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical analysis, and in particular relates to an ion chromatography method for detecting the contents of sodium, potassium, calcium and magnesium ions in an injection. Background Art

[0002] At present, the detection method of sodium, potassium, calcium and magnesium ion content is mostly atomic absorption spectrophotometry. This method is cumbersome to operate when detecting multiple elements simultaneously. It is necessary to repeatedly replace the corresponding hollow cathode lamp and wait for preheating to stabilize. The detection process is easily interfered by other factors such as background, and the accuracy is not high and the reproducibility is poor. Ion chromatography can also detect metal cations with high sensitivity and convenient operation for simultaneous detection of multiple elements, which greatly improves the detection efficiency and provides a new method for the detection of sodium, potassium, calcium and magnesium ion content in injection. Summary of the invention

[0003] The object of the present invention is to provide an ion chromatography method for detecting the content of sodium, potassium, calcium and magnesium ions in an injection.

[0004] The ion chromatography method for detecting the sodium, potassium, calcium and magnesium ion contents in the injection solution adopts a cation exchange chromatography column Dionex IonPac CS12ARFIC Analytical 4mm×250mm and a guard column Dionex IonPac CG12ARFICGuard 4mm×50mm; a 20mmol / L methanesulfonic acid solution is used as the mobile phase, isocratic elution is performed, the detector is a conductivity detector, the detection mode is suppressed conductivity detection, the column temperature is 25-40°C, the flow rate is 0.5-3ml / min, and the injection volume is 10-50μl.

[0005] The specific operation of the ion chromatography method is: accurately measure the injection test solution and the sodium, potassium, calcium and magnesium reference solution, inject them into the ion chromatograph respectively, and record the chromatogram; calculate the linear regression equation based on the concentration of the series of reference substances and the corresponding peak area, with a correlation coefficient of not less than 0.999, and use the linear regression equation to calculate the content of sodium, potassium, calcium and magnesium in the injection.

[0006] The method of the present invention is easy to operate, greatly improves the detection efficiency, and has strong specificity, good separation, high precision and accuracy, and good durability. BRIEF DESCRIPTION OF THE DRAWINGS

[0007] Figure 1 This is a typical chromatogram for detecting the content of sodium, potassium, calcium and magnesium ions in injection. DETAILED DESCRIPTION

[0008] (1) Exclusivity

[0009]

[0010] Sodium, potassium, magnesium and calcium specificity test results

[0011]

[0012] Conclusion: There is no interference in the blank solution; there is no interference in the blank excipient solution; in the reference solution, sodium, potassium, magnesium and calcium peaks appear in sequence; the theoretical plate number of the sodium peak is 6007; the resolution of the potassium peak is 6.51, and the theoretical plate number is 7702; the resolution of the magnesium peak is 8.17, and the theoretical plate number is 4033; the resolution of the calcium peak is 3.18, and the theoretical plate number is 3750. This method has good specificity.

[0013] (2) System applicability

[0014]

[0015]

[0016] Sodium System Suitability Results

[0017]

[0018] Potassium System Suitability Results

[0019]

[0020] Calcium System Suitability Results

[0021]

[0022]

[0023] Magnesium System Suitability Results

[0024]

[0025] Note: The elution order of sodium, potassium, calcium and magnesium is sodium, potassium, magnesium and calcium. The separation in the table refers to the separation from the previous adjacent peak.

[0026] Conclusion: There is no interference in the blank solution; in the 100% concentration reference solution, the minimum separation between the sodium, potassium, calcium and magnesium peaks is 3.17; the theoretical plate number of sodium is between 5969 and 6007; the theoretical plate number of potassium is between 7702 and 7741; the theoretical plate number of calcium is between 3736 and 3752; the theoretical plate number of magnesium is between 4015 and 4041; the RSDs of the peak areas of sodium, potassium, calcium and magnesium peaks are 1.1%, 1.0%, 1.0% and 1.0% respectively, and the RSDs of the retention times are all 0.1%. The method has good system applicability.

[0027] (3) Linearity and range

[0028] Solution preparation:

[0029] Linear stock solution: Accurately weigh about 152 mg of sodium chloride (NaCl), about 300 mg of potassium chloride (KCl), about 220 mg of calcium chloride (CaCl2·2H2O), and about 200 mg of magnesium chloride (MgCl2·6H2O), place in a 100 ml volumetric flask, dissolve and dilute to the scale with water, and shake well.

[0030] Accurately transfer an appropriate amount of linear reserve solution to the corresponding volumetric bottle according to the table below, dilute with water to the scale, and shake well to obtain each linear solution.

[0031] Linear Concentration level (%) Volume of linear stock solution pipetted (ml) Volumetric flask (ml) L1 50 5 100 L2 80 4 50 L3 100 5 50 L4 120 6 50 L5 150 15 100

[0032] Sodium Linearity Test Results

[0033]

[0034] Potassium linearity test results

[0035]

[0036] Calcium Linearity Test Results

[0037]

[0038]

[0039] Magnesium Linearity Test Results

[0040]

[0041] Conclusion: In the concentration range of 0.0761mg / ml (1.30mmol / L) to 0.2283mg / ml (3.91mmol / L), the correlation coefficient r of sodium is 0.9999, and the Y-axis intercept deviation is 0.3%; in the concentration range of 0.1506mg / ml (2.02mmol / L) to 0.4517mg / ml (6.06mmol / L), the correlation coefficient r of potassium is 0.9999, and the Y-axis intercept deviation is 0.5 %; in the concentration range of 0.1102mg / ml (0.75mmol / L) to 0.3306mg / ml (2.25mmol / L), the correlation coefficient r of calcium is 0.9999, and the Y-axis intercept deviation is 1.2%; in the concentration range of 0.1009mg / ml (0.50mmol / L) to 0.3027mg / ml (1.49mmol / L), the correlation coefficient r of magnesium is 0.9999, and the Y-axis intercept deviation is 0.9%. The linearity and range results of this method are good.

[0042] (4) Accuracy

[0043]

[0044]

[0045] Preparation of accuracy solution:

[0046]

[0047] Sodium - Accuracy Results

[0048]

[0049] Potassium - Accuracy Results

[0050]

[0051]

[0052] Calcium - Accuracy Results

[0053]

[0054] Magnesium - Accuracy Results

[0055]

[0056]

[0057] Conclusion: The recoveries of sodium at 80%, 100%, and 120% concentration levels were between 100.3% and 102.0%, and the RSD of the 9 recoveries was 0.6%; the recoveries of potassium at 80%, 100%, and 120% concentration levels were between 99.7% and 100.6%, and the RSD of the 9 recoveries was 0.3%; the recoveries of calcium at 80%, 100%, and 120% concentration levels were between 99.4% and 101.1%, and the RSD of the 9 recoveries was 0.6%; the recoveries of magnesium at 80%, 100%, and 120% concentration levels were between 100.5% and 101.7%, and the RSD of the 9 recoveries was 0.5%. This method has high accuracy.

[0058] (5) Repeatability and intermediate precision

[0059]

[0060] result:

[0061] Repeatability: In 6 test solutions, the RSDs of sodium, potassium, calcium and magnesium were 0.5%, 0.2%, 0 and 0.6% respectively; Intermediate precision: In 6 test solutions, the RSDs of sodium, potassium, calcium and magnesium were 0.9%, 0.2%, 0.3% and 0 respectively; In 12 test solutions, the RSDs of sodium, potassium, calcium and magnesium were 0.7%, 1.4%, 0.5% and 0.5% respectively.

[0062] Conclusion: This method has good precision.

[0063] (6) Durability

[0064] Robustness to fine-tune chromatographic conditions

[0065]

[0066] result:

[0067] Sodium Potassium Calcium Magnesium Durability System Suitability (100% STD) Results Summary Table

[0068]

[0069] Durability Test Solution (Sodium) Results Summary Table

[0070]

[0071]

[0072] Durability Test Solution (Potassium) Results Summary Table

[0073]

[0074] Durability Test Solution (Calcium) Results Summary Table

[0075]

[0076]

[0077] Durability Test Solution (Magnesium) Results Summary Table

[0078]

[0079] Conclusion: The method has good robustness when the chromatographic conditions (flow rate ±0.1 ml / min, mobile phase concentration +1 mmol / L and -2 mmol / L, column temperature +2°C, different batches of chromatographic columns) change slightly.

[0080] In summary, the sodium, potassium, calcium and magnesium ion detection method established in the present invention is rapid, highly specific, and the results are accurate and reliable, and can be used as a method for checking the sodium, potassium, calcium and magnesium ion content in injection solutions.

[0081] Depend on Figure 1 It can be seen that (1) the method has good specificity and the blank solution has no interference; sodium ion, potassium ion, magnesium ion, and calcium ion peaks appear one after another, and the minimum separation between the peaks is 3.18, which meets the separation standard requirements;

[0082] (2) When the concentration of the sodium ion standard solution was consistent with that of the sodium ion in the injection, the peak shape was frontier and the theoretical plate number was only 291. After dilution 50 times, the theoretical plate number increased to 6476, and the peak shape was better. When the concentrations of the potassium, calcium and magnesium ion standard solutions were consistent with those of the potassium, calcium and magnesium ion in the injection, the retention time of each peak was appropriate and the theoretical plate number was greater than 3000.

[0083] In summary, this method is suitable for the detection of sodium, potassium, calcium and magnesium ion contents.

Claims

1. An ion chromatography method for detecting the content of sodium, potassium, calcium and magnesium ions in an injection, characterized in that: A cation exchange chromatography column Dionex IonPac CS12A RFIC Analytical 4mm×250mm and a guard column Dionex IonPacCG12ARFIC Guard 4mm×50mm were used; 20mmol / L methanesulfonic acid solution was used as the mobile phase, isocratic elution was performed, the detector was a conductivity detector, the detection mode was suppressed conductivity detection, the column temperature was 25-40°C, the flow rate was 0.5-3ml / min, and the injection volume was 10-50μl.

2. The ion chromatography method for detecting the content of sodium, potassium, calcium and magnesium ions in an injection according to claim 1, characterized in that: The specific operation of the ion chromatography method is: accurately measure the injection test solution and the sodium, potassium, calcium and magnesium reference solution, inject them into the ion chromatograph respectively, and record the chromatogram; calculate the linear regression equation based on the concentration of the series of reference substances and the corresponding peak area, with a correlation coefficient of not less than 0.999, and use the linear regression equation to calculate the content of sodium, potassium, calcium and magnesium in the injection.

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