Method for determining content of sodium and / or potassium in compound vitamin C polyethylene glycol sodium potassium powder

Abstract

The invention provides a method for determining the content of sodium and / or potassium in compound vitamin C polyethylene glycol sodium-potassium powder. The method comprises the following steps: respectively preparing a test solution, a blank solution and a reference solution by adopting a solvent containing a lithium element; detection is carried out through an ICP-OES method, and the content of sodium and / or potassium is determined through an internal standard method. The content determination method disclosed by the invention is simple, convenient and rapid, can be used for simultaneously detecting the content of sodium and potassium, and is good in linear relation, relatively good in repeatability and precision, high in accuracy, good in solution stability and good in durability.

Description

Technical Field

[0001] The invention belongs to the technical field of drug analysis, and in particular relates to a method for determining the content of sodium and / or potassium in compound vitamin C polyethylene glycol (3350) sodium potassium powder. Background Art

[0002] Compound Vitamin C Polyethylene Glycol Sodium Potassium Powder, also known as Compound Vitamin C Polyethylene Glycol (3350) Sodium Potassium Powder, is an osmotic laxative with the trade name Moviprep, which is used for intestinal cleansing of adult patients before intestinal endoscopy and was approved by the FDA in 2006. It is sold in small bags, consisting of bags A and B, each bag A contains 2.691g sodium chloride, 1.015g potassium chloride, 7.500g sodium sulfate and 100g polyethylene glycol 3350, and bag B contains 4.700g vitamin C and 5.900g vitamin C sodium.

[0003] At present, the 2020 edition of the National Pharmacopoeia mostly uses atomic absorption spectrophotometry for the determination of sodium and potassium ions. CN113029987A discloses a method for determining the total sodium content in compound polyethylene glycol electrolyte powder using atomic absorption spectrophotometry. However, the atomic absorption method can only detect a single element at a time, which is inconvenient to operate and has low efficiency; it has weak anti-interference ability and low sensitivity; the linear range of the determination working curve is narrow and the repeatability is poor.

[0004] Inductively coupled plasma optical emission spectrometry (ICP-OES) uses inductively coupled plasma as an excitation light source to analyze the element to be tested based on the characteristic spectral lines emitted when the atoms of the element to be tested in an excited state return to the ground state. It has the advantages of high sensitivity, low detection limit, good accuracy, and a wide linear range. At present, there is no report on the determination of sodium or potassium content in compound vitamin C polyethylene glycol (3350) sodium potassium powder by inductively coupled plasma optical emission spectrometry. Therefore, it is necessary to develop an inductively coupled plasma optical emission spectrometry detection method with strong specificity, simple and rapid operation, and high sensitivity. Summary of the invention

[0005] The present invention provides a method for determining the content of sodium and / or potassium in compound vitamin C polyethylene glycol sodium potassium powder by inductively coupled plasma emission spectroscopy. The method has the advantages of simple operation, good linear relationship, good repeatability and accuracy, and can sensitively, quickly and efficiently detect the content of sodium and / or potassium in the sodium potassium powder.

[0006] To achieve the above object, the present invention is implemented through the following technical solutions:

[0007] A method for determining the content of sodium and / or potassium in compound vitamin C sodium-potassium polyethylene glycol powder comprises the following steps: using a solvent containing lithium element to prepare a test solution, a blank solution and a reference solution respectively; performing detection by an ICP-OES method, and determining the content of sodium and / or potassium by an internal standard method.

[0008] In some embodiments, the solvent is an acid solution; preferably nitric acid or hydrochloric acid; more preferably nitric acid; further preferably an aqueous solution of 2% to 5% nitric acid.

[0009] In some embodiments, the lithium element is a lithium salt; preferably one of lithium carbonate, lithium nitrate, lithium chloride, lithium sulfate or lithium acetate; more preferably lithium carbonate.

[0010] In some embodiments, the solvent contains 2 to 20 μg / mL lithium, preferably 5 to 15 μg / mL, and more preferably 10 μg / mL.

[0011] In some embodiments, the solvent preparation method is to add water to the lithium salt and nitric acid to completely dissolve the lithium carbonate, and then dilute it with water.

[0012] In some embodiments, the blank solution is blank solution 1 and blank solution 2, wherein blank solution 1 is an aqueous solution, and blank solution 2 is an aqueous solution of polyethylene glycol 3350 or an aqueous solution of vitamin C.

[0013] In some embodiments, the control solution is a solution containing sodium, potassium and polyethylene glycol 3350 or vitamin C.

[0014] In some embodiments, the optimal sensitive analysis line wavelength of the sodium element is 589.592 nm, the optimal sensitive analysis line wavelength of the potassium element is 766.490 nm, and the optimal sensitive analysis line wavelength of the lithium element is 670.784 nm.

[0015] In some embodiments, the operating parameters of ICP-OES are: RF power is 1300W~1500W; nebulizing gas flow rate is 0.50L / min~0.60L / min; auxiliary gas flow rate is 0.4L / min~0.6L / min; plasma gas flow rate is 14L / min~16L / min, and the injection rate is 1.3mL / min~1.7mL / min.

[0016] In some embodiments, the measuring instrument is Perkin Elmer Avio 200; and the observation mode is axial observation.

[0017] In some embodiments, the emission spectrum response value of each element is obtained by the ICP-OES method, and the content of the element Na or K to be measured is calculated by the internal standard method.

[0018] The calculation formula is as follows:

[0019] (i, calculate the measured values ​​of sodium or potassium in the test solution, reference solution, blank 1 and 2 respectively);

[0020]

[0021] Concentration of the element to be measured in the test solution (mg / mL) = measured value of the element to be measured in the test solution × f value (iii);

[0022] Concentration of the element to be measured in blank solution 1 (mg / mL) = measured value of the element to be measured in blank solution 1 × f value (iiii);

[0023]

[0024] In some embodiments, a method for determining the content of sodium and potassium in compound vitamin C sodium polyethylene glycol potassium powder is provided, wherein the method is used to determine the content of sodium and potassium in a bag of compound vitamin C sodium polyethylene glycol potassium powder A, wherein the test sample is a bag of compound vitamin C sodium polyethylene glycol potassium powder A, the reference solution is a mixed solution containing polyethylene glycol 3350, sodium chloride and potassium chloride, the blank solutions are blank solution 1 and blank solution 2; the blank solution 1 is an aqueous solution; the blank solution 2 is an aqueous solution of polyethylene glycol 3350.

[0025] In some embodiments, the method is used to determine the content of sodium and potassium in a bag of compound vitamin C polyethylene glycol sodium potassium powder A, and the concentration of polyethylene glycol 3350 in the reference solution is 0.5 mg / mL to 1.5 mg / mL, preferably 0.8 mg / mL to 1.2 mg / mL, and more preferably 1 mg / mL;

[0026] And / or, the sodium chloride concentration in the reference solution is 20.0 μg / mL to 140.0 μg / mL, preferably 21.0 μg / mL to 131.3 μg / mL, more preferably 43.7 μg / mL to 131.3 μg / mL, and further preferably 87.5 μg / mL;

[0027] And / or, the concentration of potassium chloride in the reference solution is 2.5 μg / mL to 20.0 μg / mL, preferably 2.5 μg / mL to 15.0 μg / mL, more preferably 5 μg / mL to 15 μg / mL, and further preferably 10 μg / mL.

[0028] In some embodiments, a method for determining the content of sodium and / or potassium in compound vitamin C sodium polyethylene glycol potassium powder is used for determining the content of sodium in compound vitamin C sodium polyethylene glycol potassium powder B bag, the test sample is compound vitamin C sodium polyethylene glycol potassium powder B bag, and the reference solution contains sodium chloride and vitamin C. In some embodiments, the blank solutions are blank solution 1 and blank solution 2; the blank solution 1 is an aqueous solution; the blank solution 2 is a vitamin C aqueous solution.

[0029] In some embodiments, the method is used to determine the sodium content in the compound vitamin C polyethylene glycol sodium potassium powder B bag, and the sodium chloride concentration in the reference solution is 20.0 μg / mL to 140.0 μg / mL, preferably 21.0 μg / mL to 131.3 μg / mL, more preferably 43.7 μg / mL to 131.3 μg / mL, and further preferably 87.5 μg / mL;

[0030] And / or, the vitamin C concentration in the reference solution is 0.2 mg / mL to 0.8 mg / mL, preferably 0.4 mg / mL to 0.6 mg / mL, and more preferably 0.5 mg / mL.

[0031] The method of the present invention further includes that the content limit should comply with the sodium content limit in bag B of 0.616 to 0.753 g / bag; and / or, the sodium content limit in bag A is 3.138 to 3.835 g / bag, and the potassium content limit is 0.500 to 0.611 g / bag.

[0032] In some specific embodiments, the method for detecting the content of sodium and potassium in the compound vitamin C polyethylene glycol sodium potassium powder A bag comprises the following steps:

[0033] (1) Preparation of solvent: Take lithium carbonate and nitric acid, add water, dissolve them, and then dilute them with water;

[0034] (2) Preparation of reference solution: adding sodium chloride, potassium chloride and polyethylene glycol 3350 to the solvent prepared in step (1) to obtain a reference solution;

[0035] (3) Preparation of blank solution: Blank solution 1 is prepared by mixing water and solvent; Blank solution 2 is prepared by adding solvent to polyethylene glycol 3350 for dilution;

[0036] (4) Preparation of test solution: Take the contents of bag A, dissolve them in water, and then dilute them with water; then add the solvent prepared in step (1) to dilute;

[0037] (5) Using inductively coupled plasma atomic emission spectrometry, the emission spectrum response values ​​of the test solution, reference solution, blank solution 1 and blank solution 2 were measured at wavelengths of 589.592 nm for sodium, 766.490 nm for potassium and 670.784 nm for lithium, respectively, with lithium as the internal standard, to calculate the contents of sodium and potassium in bag A;

[0038] The Na content calculation formula is as follows:

[0039] Calculate the Na element determination values ​​in the test solution, reference solution, blank 1 and 2 respectively;

[0040]

[0041] Na concentration of test solution (mg / mL) = measured value of Na element in test solution × f value;

[0042] Blank solution 1Na concentration (mg / mL) = blank solution 1Na element determination value × f value;

[0043]

[0044] The potassium (K) content calculation formula is calculated according to the above Na content calculation formula, with the Na concentration or response value replaced by K.

[0045] In some specific embodiments, the method for determining the sodium content in the compound vitamin C polyethylene glycol sodium potassium powder bag B comprises the following steps:

[0046] 1) Preparation of solvent: Take lithium carbonate and nitric acid, add water, dissolve, and dilute with water;

[0047] 2) Preparation of reference solution: adding sodium chloride and vitamin C to the solvent prepared in step (1) to obtain a reference solution;

[0048] 3) Preparation of blank solution: the blank solution 1 is prepared by mixing water and solvent; the blank solution 2 is prepared by adding solvent to vitamin C for dilution;

[0049] 4) Preparation of test solution: Take the contents of bag B, add water to dissolve, then dilute with water; then add the solvent prepared in step 1) to dilute;

[0050] 5) Determine by inductively coupled plasma atomic emission spectrometry, take the emission spectrum response values ​​of the test solution, reference solution, blank solution 1 and blank solution 2 at the wavelengths of 589.592nm for sodium and 670.784nm for lithium, respectively, wherein lithium is used as the internal standard for sodium, and calculate the sodium content in bag B;

[0051] The Na content calculation formula is as follows:

[0052] Calculate the Na element determination values ​​in the test solution, reference solution, blank 1 and 2 respectively;

[0053]

[0054] Na concentration of test solution (mg / mL) = measured value of Na element in test solution × f value;

[0055] Blank solution 1Na concentration (mg / mL) = blank solution 1Na element determination value × f value;

[0056]

[0057] The technical effects of the present invention are as follows:

[0058] 1 The detection method of the present invention is simple and rapid, can detect the sodium and potassium contents at the same time, has high accuracy, saves detection time, and improves detection efficiency.

[0059] 2 The solvent of the present invention adopts an acid system, especially nitric acid, to dissolve and dilute the sample, so that sodium and potassium exist in the solution in a stable form, and the sample solution has good stability.

[0060] 3 The present invention improves the accuracy of the determination method by selecting appropriate wavelengths for each element and using lithium as an internal standard, compared with not adding an internal standard element or using rubidium as an internal standard.

[0061] 4 The present invention has carried out a series of methodological verifications and meets the detection requirements: the linear relationship is good, and the correlation coefficient can reach above 0.999; the repeatability and precision are good, the accuracy is high, the solution stability is good, and the durability is good.

[0062] The term "internal standard method" means that the same concentration of internal standard element is added to the reference solution, the test solution and the blank solution, and the ratio of the emission spectrum intensity of the measured element to the emission spectrum intensity of the internal standard element is calculated to calculate the content of the measured element in the sample.

[0063] Instruction Manual

[0064] Figure 1 The spectra of the elements to be measured at different wavelengths in Example 1;

[0065] Figure 2 The element spectra of different internal standards at different wavelengths in Example 2;

[0066] Figure 3 are the emission spectra of sodium, potassium and lithium of blank solution 1 in Example 4-1;

[0067] Figure 4 are the emission spectra of sodium, potassium and lithium of blank solution 2 in Example 4-1;

[0068] Figure 5 is the emission spectra of sodium, potassium and lithium of the reference solution in Example 4-1;

[0069] Figure 6 is the emission spectra of sodium, potassium and lithium of the test solution in Example 4-1;

[0070] Figure 7 This is the linear range of the method for determining the sodium and potassium content in bag A in Example 4-2. DETAILED DESCRIPTION

[0071] The present invention is described in more detail below by way of examples, but these specific descriptions are only used to illustrate the technical solution of the present invention and do not constitute any limitation to the present invention.

[0072] The reagents and raw materials used in the present invention are all commercially available. Experimental methods without specific conditions are usually carried out under conventional conditions.

[0073] In the following examples, each bag A of the compound vitamin C polyethylene glycol (3350) sodium potassium powder contains 111.9 g of powder, specifically 2.691 g of sodium chloride, 1.015 g of potassium chloride, 7.500 g of sodium sulfate and 100 g of polyethylene glycol 3350, 0.233 g of aspartame, 0.117 g of acesulfame potassium, and 0.34 g of lemon powder flavor. Each bag B contains 10.6 g of powder, specifically 4.700 g of vitamin C and 5.900 g of vitamin C sodium.

[0074] Example 1 Selection of wavelength of the element to be measured

[0075] Reference solution: Take appropriate amount of sodium and potassium reference substances, dissolve and dilute with 2% nitric acid to make a solution containing 30 μg sodium and 5 μg potassium per 1 mL.

[0076] Using the axial observation method, take the reference solution, inject the sample for measurement, and collect the spectra of sodium at 589.592nm, 330.237nm or 588.995nm, and potassium at 766.490nm. The results are as follows Figure 1 shown.

[0077] The results showed that the peak shape was good and the response was high at the wavelengths of 589.592nm for sodium and 766.490nm for potassium.

[0078] Embodiment 2 Internal standard method determination and internal standard selection

[0079] Take lithium (Li) or rubidium (Rb) as internal standard, take appropriate amount of lithium reference substance and rubidium reference substance, dilute with 2% nitric acid to make solution with 5μg lithium or 5μg rubidium per 1mL. Use axial observation mode, take internal standard solution, inject and measure, observe the spectrum of Li at 670.784nm or 460.286nm, rubidium at 780.023nm wavelength, the result is as follows Figure 2 shown.

[0080] The results show that Li has a good peak shape and high response at a wavelength of 670.784nm, while Rb has a lower response, with a response value of only 1 / 25 of Li, and the Rb baseline is uneven with background interference.

[0081] (1) Impact on test results

[0082] Sodium reference stock solution: Take an appropriate amount of sodium reference and use 2% nitric acid to make a solution containing 150 μg of sodium per 1 mL.

[0083] Potassium reference stock solution: Take an appropriate amount of potassium reference and use 2% nitric acid to make a solution containing 25 μg of potassium per 1 mL.

[0084] Internal standard solution: Take an appropriate amount of rubidium reference substance and dilute it with 2% nitric acid to make a solution containing 100 μg of rubidium per 1 mL.

[0085] Standard curve solution: Accurately take 0mL, 5mL, 10mL, 15mL, 20mL, 25mL, and 20mL of sodium reference stock solution and potassium reference stock solution respectively, place them in the same 100mL volumetric flask, dilute to the scale with 2% nitric acid to make solutions containing 0μg, 7.5μg, 15μg, 22.5μg, 30μg, 37.5μg, and 45μg of sodium per 1mL; and 0μg, 1.25μg, 2.5μg, 3.75μg, 5μg, 6.25μg, and 7.5μg of potassium per 1mL.

[0086] Blank auxiliary material ①: Take 1.015g potassium chloride, 100g polyethylene glycol 3350, 0.233g aspartame, 0.117g acesulfame potassium, and 0.34g lemon powder flavor, mix well, and obtain.

[0087] Blank auxiliary material ②: Take 2.691g sodium chloride, 7.500g sodium sulfate and 100g polyethylene glycol 3350, 0.233g aspartame, 0.117g acesulfame potassium, and 0.34g lemon powder flavor, mix well, and obtain.

[0088] Blank auxiliary material mother solution ①: Take 1 g of the above blank auxiliary material ①, dissolve it in 2% nitric acid and dilute it to 50 mL.

[0089] Blank auxiliary material mother solution ②: Take 1 g of the above blank auxiliary material ②, dissolve it in 2% nitric acid and dilute it to 50 mL.

[0090] Sodium spike recovery solution: Take 5 mL of blank auxiliary material mother solution ① and 5 mL of internal standard solution and put them into 100 mL volumetric flask, make 4 parallel portions, then accurately add 0 mL, 15 mL, 20 mL, and 25 mL of sodium reference stock solution respectively, dilute to the scale with 2% nitric acid, mix well to obtain blank auxiliary material solution, 75% recovery solution, 100% recovery solution, and 125% recovery solution.

[0091] Potassium spiked recovery solution: Take 5 mL of blank auxiliary material mother solution ② and 5 mL of internal standard solution and place them in a 100 mL volumetric flask, make 4 parallel portions, then accurately add 0 mL, 15 mL, 20 mL, and 25 mL of potassium reference stock solution respectively, dilute to the scale with 2% nitric acid, mix well to obtain blank auxiliary material solution, 75% recovery solution, 100% recovery solution, and 125% recovery solution.

[0092] Axial observation was adopted, and the wavelengths of rubidium at 780.023nm, sodium at 589.592nm, and potassium at 766.490nm were measured. The above standard curve solution and recovery solution were taken for sample measurement. The concentration of each solution was calculated by the internal standard correction method, and the recovery rate of each solution was calculated. The results are shown in Tables 1 and 2.

[0093] The results showed that using Rb as the internal standard, the sodium recovery rate was good, but the potassium recovery rate was low.

[0094] Table 1 Sodium recovery results with Rb as internal standard

[0095]

[0096] Table 2 Potassium recovery results with Rb as internal standard

[0097]

[0098] Example 3 Selection of observation method

[0099] When using the radial observation method, the sensitivity of sodium, potassium and lithium elements is low, and the stability of the emission spectrum of the elements to be measured is poor; while choosing the axial observation method, the measurement stability is improved, making the measurement result highly sensitive.

[0100] Example 4 Determination of sodium and potassium content in bag A of compound vitamin C polyethylene glycol (3350) sodium and potassium powder

[0101] Example 4-1 Determination method

[0102] 1. Preparation of solvent

[0103] Take 260 mg of lithium carbonate and 100 mL of nitric acid, put them in the same beaker, add 1 L of water to completely dissolve the lithium carbonate, then dilute to 5 L with water and mix well to obtain a solvent containing 10 μg of internal standard lithium per 1 mL. Finally, the solvent contains 2% nitric acid.

[0104] 2. Preparation of reference substance stock solution

[0105] (1) Prepare sodium reference stock solution: accurately weigh 350 mg of sodium chloride reference solution and place in a 200 mL volumetric flask. Dissolve and dilute to volume with solvent and shake well.

[0106] (2) Preparation of potassium reference stock solution: accurately weigh 200 mg of potassium chloride reference solution, place in a 50 mL volumetric flask, dissolve and dilute to the mark with solvent, and shake well; accurately weigh 10 mL of potassium chloride reference solution, place in a 200 mL volumetric flask, dissolve and dilute to the mark with solvent, and shake well.

[0107] 3. Preparation of reference solution

[0108] Accurately measure 5 mL of sodium reference stock solution, 5 mL of potassium reference stock solution and 5 mL of polyethylene glycol 3350 mother solution (take an appropriate amount of polyethylene glycol 3350, dissolve it in water and dilute it to make a solution containing 20 mg per 1 mL), place them in the same 100 mL volumetric flask, dilute to the scale with solvent, and shake well.

[0109] 4. Preparation of blank solution

[0110] Preparation of blank solution 1: Accurately measure 5 mL of water, place in a 100 mL volumetric flask, dilute to the scale with solvent, and shake well.

[0111] Preparation of blank solution 2: Accurately measure 5 mL of polyethylene glycol 3350 mother solution (take an appropriate amount of polyethylene glycol 3350, dissolve it in water and dilute it to make a solution containing 20 mg per 1 mL), place it in a 100 mL volumetric flask, dilute it to the scale with solvent, and shake well.

[0112] 5. Preparation of test solution

[0113] Take the contents of bag 4 of bag A, place in a 2000mL volumetric flask, add appropriate amount of water, shake to dissolve, cool, dilute to scale with water, shake well, and use as test solution 1. Accurately measure 5mL of test solution 1, place in a 50mL volumetric flask, dilute to scale with water, shake well. Accurately measure 5mL again, place in a 100mL volumetric flask, dilute to scale with solvent, and shake well.

[0114] 6 Determined by inductively coupled plasma atomic emission spectrometry.

[0115] Table 3 ICP-OES instrument operating parameters

[0116]

[0117] Take the above test solution, reference solution, blank solution 1 and blank solution 2 and inject them respectively, and obtain the emission spectrum response values ​​of each solution at the wavelength of 589.592nm for sodium, 766.490nm for potassium and 670.784nm for lithium. The results are shown in Figure 3 , Figure 4 , Figure 5 and Figure 6 Sodium and potassium are calculated with lithium as the internal standard.

[0118] The Na content is calculated as follows:

[0119] pass The Na element determination values ​​in the test solution, reference solution, blank solution 1 and blank solution 2 were calculated respectively.

[0120]

[0121] Na concentration of test solution (mg / mL) = measured value of Na element in test solution × f value;

[0122] Blank solution 1Na concentration (mg / mL) = blank solution 1Na element determination value × f value;

[0123]

[0124] The potassium (K) content calculation formula is as follows: according to the above Na content calculation formula, replace the Na concentration or response value with K for calculation.

[0125] 7.3 Batch assay results

[0126] Different batches of compound vitamin C polyethylene glycol (3350) sodium potassium powder samples were taken, and the content determination results are shown in Table 4.

[0127] Table 4 Determination results of sodium and potassium content in different batches of A bags

[0128]

[0129] Example 4-2 Verification of the method for determining the sodium and potassium content in bag A of compound vitamin C polyethylene glycol (3350) sodium and potassium powder

[0130] 1Linear range

[0131] The preparation methods of solvent, polyethylene glycol 3350 mother solution, sodium reference substance stock solution and potassium reference substance stock solution are the same as those in Example 4-1.

[0132] Mixed reference substance stock solution: Accurately measure 50 mL of sodium reference substance stock solution and 50 mL of potassium reference substance stock solution respectively, put them into the same 200 mL, dilute to the scale with solvent, shake well, and obtain.

[0133] Series of reference substance solutions: Accurately measure 5 mL of polyethylene glycol 3350 mother solution and place it in a 100 mL volumetric flask, make 7 parallel portions, then accurately add 0 mL, 5 mL, 10 mL, 15 mL, 20 mL, 25 mL, and 30 mL of the mixed reference substance stock solution, dilute to the scale with solvent, and shake well to obtain STD-0% (Blank), STD-25%, STD-50%, STD-75%, STD-100%, STD-125%, and STD-150% solutions.

[0134] Take the above series of reference solution, inject and measure respectively according to the law, record the measured values ​​of sodium, potassium and lithium (internal standard), use the concentration as the horizontal axis (x) and the measured value (response value cps of the element to be measured / response value cps of the internal standard) as the vertical axis (y), draw the standard curve, and calculate the regression equation. The linear determination results are shown in Figure 7 .

[0135] 2 Accuracy

[0136] The preparation methods of solvent, polyethylene glycol 3350 mother solution, sodium reference substance stock solution, potassium reference substance stock solution and reference substance solution are the same as those of Example 4-1, wherein sodium reference substance stock solution, potassium reference substance stock solution and reference substance solution are prepared in parallel in 2 portions respectively.

[0137] Blank solution: Take 5 mL of polyethylene glycol 3350 mother solution, place it in a 100 mL volumetric flask, dilute to the scale with solvent, shake well, and prepare a blank solution.

[0138] Flavoring agent solution: according to the prescription ratio, take 0.583g of aspartame, 0.293g of acesulfame potassium, and 0.850g of lemon powder flavor, mix well, put into the same 250mL volumetric flask, dissolve and dilute to the scale with water, and shake well.

[0139] Test solution: Take 10g of polyethylene glycol 3350 and 10mL of flavoring solution, place them in the same 50mL volumetric flask, dissolve and dilute to the scale with water, and shake well; then accurately measure 5mL, place it in a 50mL volumetric flask, dilute to the scale with water, and shake well; then accurately measure 5mL, place it in a 100mL volumetric flask, dilute to the scale with solvent, and shake well.

[0140] Blank control solution: Accurately measure 5 mL of water, place it in a 100 mL volumetric flask, dilute to the scale with solvent, shake well, and prepare a blank control solution.

[0141] 80% recovery solution: Take 10g of polyethylene glycol 3350, 10mL of flavoring solution, 0.600g of sodium sulfate reference substance, 0.215g of sodium chloride reference substance, and 0.081g of potassium chloride reference substance, place them in the same 50mL volumetric flask, dissolve and dilute to the mark with water, and shake well; then accurately measure 5mL, place it in a 50mL volumetric flask, dilute to the mark with water, and shake well; then accurately measure 5mL, place it in a 100mL volumetric flask, dilute to the mark with solvent, and shake well. Prepare 3 copies in parallel.

[0142] 100% recovery solution: Take 10g of polyethylene glycol 3350, 10mL of flavoring solution, 0.750g of sodium sulfate reference substance, 0.269g of sodium chloride reference substance, and 0.102g of potassium chloride reference substance, place them in the same 50mL volumetric flask, dissolve and dilute to the mark with water, and shake well; then accurately measure 5mL, place it in a 50mL volumetric flask, dilute to the mark with water, and shake well; then accurately measure 5mL, place it in a 100mL volumetric flask, dilute to the mark with solvent, and shake well. Prepare 3 copies in parallel.

[0143] 120% recovery solution: Take 10g of polyethylene glycol 3350, 10mL of flavoring solution, 0.900g of sodium sulfate reference substance, 0.323g of sodium chloride reference substance, and 0.122g of potassium chloride reference substance, place them in the same 50mL volumetric flask, dissolve and dilute to the mark with water, and shake well; then accurately measure 5mL, place it in a 50mL volumetric flask, dilute to the mark with water, and shake well; then accurately measure 5mL, place it in a 100mL volumetric flask, dilute to the mark with solvent, and shake well. Prepare 3 copies in parallel.

[0144] The above solutions were taken and measured according to the law, and the recovery rates of sodium and potassium elements were calculated. The results are shown in Table 5 below. The results show that the method has good accuracy.

[0145] Table 5 Accuracy test results

[0146]

[0147] 3. Precision

[0148] (1) Injection precision

[0149] The STD-100% reference solution under the "Linearity and Range" item in Example 4-2 was sampled 6 times in succession. The results showed that the RSD of the injection precision of sodium and potassium elements was no more than 1.6%, indicating that the injection precision was good.

[0150] (2) Repeatability

[0151] Reference solution: Take the "reference solution" under "Accuracy" in Example 4-2.

[0152] According to the method in Example 4-1, blank solution 1 and test solution were prepared respectively, and 6 test solution were prepared in parallel. The content of sodium and potassium impurities was determined. The results showed that the RSD of the sodium and potassium content of the 6 test solutions was no more than 1.3%, and the repeatability of the method was good.

[0153] (3) Intermediate precision

[0154] Six samples were prepared by different experimenters at different times according to the sample preparation method under the "Repeatability" item in Example 4-2, and the same method was used for determination. The results of 12 determinations (n=12) showed that the RSDs of the sodium and potassium contents were no more than 1.4%, and the intermediate precision of the method was good.

[0155] 4 Solution stability

[0156] Take the 100% reference solution under the "Linearity and Range" item and the test solution under the "Repeatability" item in Example 4-2, and place them at room temperature for 24 hours and 72 hours before measuring. The results are shown in Tables 6 and 7.

[0157] Table 6 Stability test results of reference solution

[0158]

[0159] Table 7 Stability test results of the test solution

[0160]

[0161] 5. Durability

[0162] The ICP-OES determination parameters were appropriately adjusted (durability condition see 0), blank solution, reference solution and test solution were sampled and measured, and the response value (cps) of each element in each solution was recorded. The content under each change condition was investigated, and the test results are shown in Table 9.

[0163] Table 8 Durability test conditions

[0164]

[0165]

[0166] Table 9 Durability test results

[0167]

[0168] 6. Exclusivity

[0169] Take the blank solution (0% reference solution) and 25% reference solution under "Linearity and Range in Example 4-2", measure according to the law, and record the emission spectrum intensity of sodium at 589.592nm and potassium at 766.490nm. Visually compare the spectra of the reference solution and the blank solution at 589.592nm and 766.490nm.

[0170] The results showed that the blank solution did not interfere with the determination at the wavelengths of 589.592nm for sodium and 766.490nm for potassium.

[0171] Example 4-3

[0172] Refer to the method under "Accuracy" in Example 4-2, except that 5% nitric acid is used as the solvent. The results are shown in Tables 10 and 11. The results show that the method has good accuracy when 5% nitric acid is used as the solvent.

[0173] Table 10 5% nitric acid as solvent sodium content accuracy test results

[0174]

[0175] Table 11 Results of potassium content accuracy determination using 5% nitric acid as solvent

[0176]

[0177]

[0178] Therefore, the sample was acidified with nitric acid to make the sample stable and completely dissolved with high accuracy.

[0179] Example 5 Effect of using water as solvent on test results

[0180] 1. Preparation of solvent

[0181] The solvent was prepared with water. The specific steps were as follows: 260 mg of lithium carbonate was added to 1 L of water to completely dissolve the lithium carbonate, and then diluted to 5 L with water and mixed to obtain a solvent containing 10 μg of internal standard lithium per 1 mL.

[0182] 2. Plotting the reference solution curve

[0183] The preparation methods of the remaining polyethylene glycol 3350 mother solutions, sodium reference substance stock solutions, potassium reference substance stock solutions, mixed reference substance stock solutions, and series reference substance solutions and the drawing of standard curves are the same as those in the "Linearity and Range" item in Example 4-2.

[0184] The results showed that the correlation coefficient of the standard curve of the Na element was 0.9997; the correlation coefficient of the standard curve of the K element was 0.8175, which was not a linear relationship. Therefore, potassium was unstable when prepared with water as the solvent.

[0185] 3. Accuracy

[0186] The solvent was changed from nitric acid to water, and the rest was based on the experimental method of "Accuracy" in Example 4-2.

[0187] The results showed that the recovery rate of sodium spike was 85.8%, which was not very accurate.

[0188] Example 6 Determination of sodium and potassium content in bag A without using internal standard method

[0189] 1. Preparation of solvent

[0190] Take 100 mL of nitric acid, place it in a beaker, add water to dilute to 5 L, mix well, and the solvent contains 2% nitric acid.

[0191] 2. Sodium reference stock solution: Take an appropriate amount of sodium reference and use 2% nitric acid to make a solution containing 150 μg of sodium per 1 ml.

[0192] Potassium reference stock solution: Take an appropriate amount of potassium reference and use 2% nitric acid to make a solution containing 25 μg of potassium per 1 ml.

[0193] 3 Standard curve solution: Accurately take 0ml, 5ml, 10ml, 15ml, 20ml, 25ml, and 20ml of the sodium reference stock solution and the potassium reference stock solution respectively, put them in the same 100ml volumetric flask, dilute to the scale with 2% nitric acid to make solutions containing 0μg, 7.5μg, 15μg, 22.5μg, 30μg, 37.5μg, and 45μg of sodium per 1ml; and 0μg, 1.25μg, 2.5μg, 3.75μg, 5μg, 6.25μg, and 7.5μg of potassium.

[0194] Blank auxiliary material ①: Take 1.015g potassium chloride, 100g polyethylene glycol 3350, 0.233g aspartame, 0.117g acesulfame potassium, and 0.34g lemon powder flavor, mix well, and obtain.

[0195] Blank auxiliary material ②: Take 2.691g sodium chloride, 7.500g sodium sulfate and 100g polyethylene glycol 3350, 0.233g aspartame, 0.117g acesulfame potassium, and 0.34g lemon powder flavor, mix well, and obtain.

[0196] Blank auxiliary material mother solution ①: Take 1g of the above blank auxiliary material ①, dissolve it in 2% nitric acid and dilute it to 50ml.

[0197] Blank auxiliary material mother solution ②: Take 1g of the above blank auxiliary material ②, dissolve it in 2% nitric acid and dilute it to 50ml.

[0198] Sodium spiked recovery solution: Take 5 ml of blank auxiliary material mother solution ① and 5 ml of internal standard solution and put them into 100 ml volumetric flasks, make 4 parallel portions, then accurately add 0 ml, 15 ml, 20 ml and 25 ml of sodium reference stock solution respectively, dilute to the scale with 2% nitric acid, mix well to obtain blank auxiliary material solution, 75% recovery solution, 100% recovery solution and 125% recovery solution.

[0199] Potassium spiked recovery solution: Take 5 ml of blank auxiliary material mother solution ② and 5 ml of internal standard solution and put them into 100 ml volumetric flasks, make 4 parallel portions, then accurately add 0 ml, 15 ml, 20 ml and 25 ml of potassium reference stock solution respectively, dilute to the scale with 2% nitric acid, mix well to obtain blank auxiliary material solution, 75% recovery solution, 100% recovery solution and 125% recovery solution.

[0200] 3 Determined by inductively coupled plasma atomic emission spectrometry. The inductively coupled plasma atomic emission spectrometer and ICP-OES instrument parameters (injection rate, observation mode, plasma gas flow rate, auxiliary gas flow rate, atomizing gas flow rate, radio frequency power) are the same as those in Example 4-1.

[0201] 4 Take the above standard curve solution and recovery solution, and measure at 589.592nm for sodium and 766.490nm for potassium. Calculate according to the standard curve method (i.e., bring the response value of the recovery solution into the corresponding standard curve), and calculate the recovery of each solution.

[0202] The specific calculation results are shown in Table 12 and Table 13. The results show that the potassium recovery rate is high.

[0203] Table 12

[0204]

[0205] Table 13

[0206]

[0207] Example 7A Effect of the preparation of reference solution on the experimental results in the determination of bag content

[0208] The mother solution of polyethylene glycol 3350 was not added in the preparation of the reference solution, and the rest of the method was the same as Example 4-1. The results showed that since polyethylene glycol 3350 is a polymer, the concentration of polyethylene glycol 3350 in the test solution was 1 mg / mL, and the viscosity of the solution was relatively high, which seriously affected the atomization detection of the sample, and the matrix effect caused inaccurate detection results.

[0209] Example 8 Determination of the content of sodium in bag B of compound vitamin C polyethylene glycol (3350) sodium potassium powder

[0210] Example 8-1 Determination method

[0211] 1. Preparation of solvent

[0212] Take 260 mg of lithium carbonate and 100 mL of nitric acid, put them in the same beaker, add 1 L of water to completely dissolve the lithium carbonate, then dilute to 5 L with water and mix well to obtain a solvent containing 10 μg of internal standard lithium per 1 mL.

[0213] Preparation of 2-sodium reference stock solution

[0214] Take 350 mg of sodium chloride reference substance, weigh accurately, place in a 200 mL volumetric flask, dissolve and dilute to the scale with solvent, and shake well.

[0215] 3. Preparation of reference solution

[0216] Accurately measure 5 mL of sodium reference stock solution and 5 mL of vitamin C mother solution (take an appropriate amount of vitamin C, dissolve it in water and dilute it to make a solution containing 10 mg of vitamin C per 1 mL), place them in the same 100 mL volumetric flask, dilute to the scale with solvent, and shake well.

[0217] 4. Preparation of blank solution

[0218] Preparation of blank solution 1: Accurately measure 5 mL of water, place in a 100 mL volumetric flask, dilute to the scale with solvent, and shake well.

[0219] Preparation of blank solution 2: Accurately measure 5 mL of vitamin C mother solution, place it in the same 100 mL volumetric flask, dilute to the scale with solvent, and shake well.

[0220] 5. Preparation of test solution

[0221] Take the contents of 4 bags of bag B of this product, place them in a 1000mL volumetric flask, add appropriate amount of water, shake to dissolve, cool, dilute to scale with water, shake well, and use as the test solution (2). Accurately measure 5mL, place them in a 20mL volumetric flask, dilute to scale with water, shake well; accurately measure 5mL again, place them in a 100mL volumetric flask, dissolve with solvent and dilute to scale, shake well.

[0222] 6 Determined by inductively coupled plasma atomic emission spectrometry.

[0223] The specific parameters are the same as those in Example 4-1.

[0224] The test solution, reference solution, blank solution 1 and blank solution 2 were injected respectively, and the emission spectrum response values ​​of each solution measured at the wavelength of 589.592nm for sodium and 670.784nm for lithium were obtained respectively, and the calculation was performed with lithium as the internal standard.

[0225] Na content calculation formula

[0226]

[0227] The calculation formulas for the Na concentration of the test solution and the Na concentration of the blank solution are consistent with those in Example 4-1.

[0228] 7 Results of content determination of 3 batches in pilot test

[0229] Different batches of compound vitamin C polyethylene glycol (3350) sodium potassium powder samples were taken, and the content determination results are shown in Table 14.

[0230] Table 14 Determination results of sodium content in different batches of B

[0231] Sodium content in bag B (g / bag) batch Sodium Content 1 0.675 2 0.677 3 0.684

[0232] Example 8-2 Verification of the method for determining the content of sodium in bag B of compound vitamin C polyethylene glycol (3350) sodium potassium powder

[0233] Referring to the specific experiment of Example 8-1 and the methodological verification method of Example 4-2, the methodological verification of the content analysis of sodium in bag B was carried out.

[0234] 1 Linearity and range

[0235] The results showed that when the sodium element was in the range of 0 to 150% of the limit concentration, a standard curve was drawn with the measured value as the ordinate (y) and the concentration as the abscissa (x). The results showed a good linear relationship, specifically, the linear range was 0 to 51.88 mg / L, the linear equation was y=0.005717x+0.001871, and the correlation coefficient r was 0.9998.

[0236] 2 Accuracy

[0237] Sodium was prepared in triplicate at three concentration levels of 80%, 100% and 120% for each concentration, and the recovery RSD (n=9) was calculated. The results showed that the average recovery was 100.0% and the RSD was 1.1%, indicating that the method had good accuracy.

[0238] 3. Precision

[0239] (1) Injection precision

[0240] A reference solution equivalent to 100% of the limit concentration was injected six times in succession. The results showed that the RSD of the injection precision of the sodium element was 1.0%, indicating that the injection precision was good.

[0241] (2) Repeatability

[0242] Six test sample solutions were prepared in parallel and the RSD of the content was calculated. The results showed that the RSD of the sodium content of the six test samples was 0.7%, and the method had good repeatability.

[0243] (3) Intermediate precision

[0244] Six samples were prepared by different experimenters at different times according to the sample preparation method under the "Repeatability" item. The results of 12 measurements (n=12) showed that the RSD of the sodium content of the test sample was 0.8%, and the intermediate precision was good.

[0245] 4 Solution stability

[0246] The sodium concentration of the reference solution and the test solution was measured after being placed at room temperature for 24 hours and 48 hours, and the ratios with the values ​​at 0 hours were 98.6%-100.1% and 97.6%-99.7%, respectively, indicating that the reference solution was stable at room temperature.

[0247] 5. Durability

[0248] Appropriately changing the nebulizer gas flow rate ±0.05L / min, plasma gas flow rate ±1L / min, radio frequency power ±100W, and injection rate ±0.2mL / min, the ratio of the content under different conditions to the content under standard conditions was between 95.0% and 105.0%, and the method had good durability.

[0249] 6. Exclusivity

[0250] Visual method, blank control solution does not interfere with the determination at the wavelength of 589.592nm for sodium.

[0251] Example 9 Effect of the Preparation of Reference Solution on the Experimental Results in the Determination of Sodium Content in Bag B

[0252] Preparation of reference solution (without vitamin C): 5 mL of sodium reference stock solution was accurately measured and placed in the same 100 mL volumetric flask, diluted to scale with solvent, and shaken. The rest of the experimental methods refer to the experimental methods of "Accuracy" in Example 4-2 to determine the recovery rate. The results are shown in Table 15.

[0253] Table 15 Accuracy results of reference solution without VC

[0254]

[0255] The results showed that when measuring the sodium content, due to the large amount of vitamin C in the matrix of the test solution, it would directly affect the atomization injection of the sample solution, produce a strong matrix effect, and lead to large detection errors.

Claims

1. A method for determining the content of sodium and / or potassium in compound vitamin C sodium and potassium polyethylene glycol powder, comprising the following steps: The test solution, blank solution and reference solution were prepared respectively using a solvent containing lithium element; the ICP-OES method was used for detection, and the content of sodium and / or potassium was determined by the internal standard method.

2. The content determination method according to claim 1, characterized in that: The solvent is an acid solution; preferably nitric acid or hydrochloric acid; more preferably nitric acid; further preferably an aqueous solution of 2% to 5% nitric acid; And / or, the lithium element is a lithium salt; preferably one of lithium carbonate, lithium nitrate, lithium chloride, lithium sulfate or lithium acetate; more preferably lithium carbonate; And / or, the solvent contains 2 to 20 μg / mL lithium, preferably 5 to 15 μg / mL, more preferably 10 μg / mL.

3. The content determination method according to claim 1, characterized in that: The blank solutions are blank solution 1 and blank solution 2, wherein blank solution 1 is an aqueous solution, and blank solution 2 is an aqueous solution of polyethylene glycol 3350 or an aqueous solution of vitamin C; the reference solution is a solution containing sodium, potassium and polyethylene glycol 3350 or vitamin C.

4. The content determination method according to claim 1, characterized in that: The best sensitive analysis line wavelength of the sodium element is 589.592 nm, the best sensitive analysis line wavelength of the potassium element is 766.490 nm, and the best sensitive analysis line wavelength of the lithium element is 670.784 nm.

5. The content determination method according to claim 1, characterized in that: The operating parameters of the ICP-OES are: RF power of 1300W to 1500W; nebulizing gas flow rate of 0.50 to 0.60L / min; auxiliary gas flow rate of 0.4 to 0.6L / min; plasma gas flow rate of 14 to 16L / min, and injection speed of 1.3 to 1.7mL / min; And / or, the measuring instrument is Perkin Elmer Avio 200; and the observation method is axial observation.

6. The content determination method according to claim 3, characterized in that: The emission spectrum response value of each element is obtained by the ICP-OES method, and the content of the element Na or K to be measured is calculated by the internal standard method. The calculation formula is as follows: (i, calculate the measured values ​​of sodium or potassium in the test solution, reference solution, blank 1 and 2 respectively); Concentration of the element to be measured in the test solution (mg / mL) = measured value of the element to be measured in the test solution × f value (iii); Concentration of the element to be measured in blank solution 1 (mg / mL) = measured value of the element to be measured in blank solution 1 × f value (iiii); 7. The content determination method according to claim 1, characterized in that: The method is used to determine the content of sodium and potassium in a bag of compound vitamin C sodium potassium polyethylene glycol powder A, the test sample is a bag of compound vitamin C sodium potassium polyethylene glycol powder A, the reference solution is a mixed solution containing polyethylene glycol 3350, sodium chloride and potassium chloride, and the blank solutions are blank solution 1 and blank solution 2; The blank solution 1 is an aqueous solution; the blank solution 2 is an aqueous solution of polyethylene glycol 3350. And / or, the concentration of polyethylene glycol 3350 in the reference solution is 0.5 mg / mL to 1.5 mg / mL, preferably 0.8 mg / mL to 1.2 mg / mL, more preferably 1 mg / mL; And / or, the sodium chloride concentration in the reference solution is 20 μg / mL to 140 μg / mL, preferably 21 μg / mL to 126 μg / mL, more preferably 43.75 μg / mL to 131.25 μg / mL, and further preferably 87.5 μg / mL; and / or, the potassium chloride concentration in the reference solution is 2.5 μg / mL to 20 μg / mL, preferably 2.5 μg / mL to 15 μg / mL, more preferably 5 μg / mL to 15 μg / mL, and further preferably 10 μg / mL.

8. The content determination method according to claim 1, characterized in that: The method is used to determine the sodium content in compound vitamin C sodium potassium polyethylene glycol powder B bag, the test sample is compound vitamin C sodium potassium polyethylene glycol powder B bag, and the reference solution contains sodium chloride and vitamin C; And / or, the blank solution is blank solution 1 and blank solution 2; the blank solution 1 is an aqueous solution; the blank solution 2 is a vitamin C aqueous solution; And / or, the sodium chloride concentration in the reference solution is 20 μg / mL to 140 μg / mL, preferably 21 μg / mL to 126 μg / mL, more preferably 43.75 μg / mL to 131.25 μg / mL, and further preferably 87.5 μg / mL; and / or, the vitamin C concentration in the reference solution is 0.25 mg / mL to 0.75 mg / mL, preferably 0.4 mg / mL to 0.6 mg / mL, and more preferably 0.5 mg / mL.

9. The content determination method according to claim 1, characterized in that: The method further includes that the content limit should comply with the sodium content limit of bag B, which is 0.616 to 0.753 g / bag; And / or, the sodium content limit in bag A is 3.138-3.835 g / bag, and the potassium content limit is 0.500-0.611 g / bag.

10. A method for detecting the content of sodium and potassium in a bag of compound vitamin C sodium potassium polyethylene glycol powder A, comprising the following steps: (1) Preparation of solvent: Take lithium carbonate and nitric acid, add water, dissolve them, and then dilute them with water; (2) Preparation of reference solution: adding sodium chloride, potassium chloride and polyethylene glycol 3350 to the solvent prepared in step (1) to obtain a reference solution; (3) Preparation of blank solution: Blank solution 1 is prepared by mixing water and solvent; Blank solution 2 is prepared by adding solvent to polyethylene glycol 3350 for dilution; (4) Preparation of test solution: Take the contents of bag A, dissolve them in water, and then dilute them with water; then add the solvent prepared in step (1) to dilute; (5) using inductively coupled plasma atomic emission spectrometry, the emission spectrum response values ​​of the test solution, reference solution, blank solution 1 and blank solution 2 were measured at wavelengths of 589.592 nm for sodium, 766.490 nm for potassium and 670.784 nm for lithium, respectively, with lithium being used as the internal standard, and the sodium and potassium contents in bag A were calculated; The Na content calculation formula is as follows: Calculate the Na element determination values ​​in the test solution, reference solution, blank 1 and 2 respectively; Na concentration of test solution (mg / mL) = measured value of Na element in test solution × f value; Blank solution 1Na concentration (mg / mL) = blank solution 1Na element determination value × f value; The potassium (K) content calculation formula is calculated according to the above Na content calculation formula, except that the Na concentration or response value is replaced by K for calculation; And / or, a method for measuring the sodium content in a bag of compound vitamin C sodium potassium polyethylene glycol powder B, comprising the following steps: 1) Preparation of solvent: Take lithium carbonate and nitric acid, add water, dissolve, and dilute with water; 2) Preparation of reference solution: adding sodium chloride and vitamin C to the solvent prepared in step 1) to obtain a reference solution; 3) Preparation of blank solution: the blank solution 1 is prepared by mixing water and solvent; the blank solution 2 is prepared by adding solvent to vitamin C for dilution; 4) Preparation of test solution: Take the contents of bag B, add water to dissolve, then dilute with water; then add the solvent prepared in step 1) to dilute; 5) Determine by inductively coupled plasma atomic emission spectrometry, take the emission spectrum response values ​​of the test solution, reference solution, blank solution 1 and blank solution 2 at the wavelengths of 589.592nm for sodium and 670.784nm for lithium, respectively, wherein lithium is used as the internal standard for sodium, and calculate the sodium content in bag B; The Na content calculation formula is as follows: Calculate the Na element determination values ​​in the test solution, reference solution, blank 1 and 2 respectively; Na concentration of test solution (mg / mL) = measured value of Na element in test solution × f value; Blank solution 1Na concentration (mg / mL) = blank solution 1Na element determination value × f value;

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