Method for detecting content of diboron trioxide

Abstract

The invention belongs to the technical field of glass container detection, and particularly relates to a method for detecting the content of diboron trioxide in medicinal glass. The invention aims to solve the problems in the prior art and provides a stable, accurate, simple and convenient diboron trioxide detection method.

Description

1. Technical field

[0001] The invention belongs to the technical field of glass container detection, and particularly relates to a method for detecting the content of boron trioxide in pharmaceutical glass. 2. Background technology

[0002] Pharmaceutical glass is a glass material or product with good chemical stability and transparency, and can stably store pharmaceutical products. For the pharmaceutical glass industry, pharmaceutical packaging materials are directly related to the quality and safety of drugs and the health of the people, and have always been a key industry regulated by the state.

[0003] According to national standards, the boron trioxide content of high borosilicate glass is ≥12%, the boron trioxide content of medium borosilicate glass is ≥8%, the boron trioxide content of low borosilicate glass is ≥5%, and the boron trioxide content of soda-lime glass is <5%. Boron trioxide (boron oxide, B2O3) has good fluxing properties and can reduce the thermal expansion coefficient and high-temperature viscosity of glass, so that glass bottles have good heat resistance, chemical stability and mechanical strength, extend service life, and improve the appearance texture. Boron trioxide can not only participate in the formation of glass, but also change the properties of glass. In addition, the Chinese Pharmacopoeia "9622 Guiding Principles for Glass Materials and Containers for Pharmaceutical Packaging" clearly states that the boron trioxide content is used to characterize the material and formula stability of borosilicate glass. The content of boron trioxide in borosilicate glass is generally above 5%. Referring to the determination method of the boron trioxide content in glass (General Rule 4203), the boron trioxide content should meet the requirements and its fluctuation range should be paid attention to.

[0004] Generally speaking, pharmaceutical glass usually contains silicon dioxide, boron trioxide, aluminum trioxide, sodium oxide, potassium oxide, calcium oxide, magnesium oxide and other ingredients. The proportion of each ingredient is not constant and fluctuates within a certain range. The chemical composition of glass varies from glass manufacturer to glass manufacturer. Glass packaging containers are usually produced by molding and tube forming processes. Different production processes have different effects on the quality of glass products, especially on the tolerance of the inner surface of the glass. Even if the same batch of glass tubes provided by the same manufacturer are used, there may be quality differences in tube glass containers, which will bring different risks to the packaged drugs.

[0005] The method for determining the content of boron trioxide in conventional pharmaceutical glass packaging materials is "YBB00232003 Boron Trioxide Determination Method", and the principle of the method is mannitol-enhanced acid-base titration, that is, the glass sample is ground and dried, melted with alkali and decomposed with acid, calcium carbonate is added to make boron form water-soluble calcium borate and separated from other impurity elements, mannitol is added to convert it into alcohol boric acid, phenolphthalein is used as an indicator, and sodium hydroxide is used to titrate and calculate the content of boron trioxide; this method is cumbersome, has many steps, and takes a long time for sample pretreatment. The single sample processing time is more than 4 hours, the titration process is long, the preparation of the titrant and indicator solution is complicated, and the volumetric test results are greatly affected by human factors.

[0006] At present, there are many reports on the methods of detecting boron trioxide in glass, which are optimized in the pretreatment process and detection method. Compared with the national standard volumetric method, the operation steps are optimized to varying degrees, and the accuracy and precision of the detection are improved. The pretreatment method generally adopts the alkali fusion method / acid decomposition method. The document "Determination of boron and other common elements in silicate glass by inductively coupled plasma atomic emission spectrometry", Guo Zhongbao et al., Rock and Mineral Testing, Vol. 34, No. 1, January 2015, uses potassium hydroxide alkali fusion method for sample preparation, in which potassium hydroxide is melted at 600-650℃ for 15-20min and then cooled, the melt is leached with hot water, and the sample is dissolved with hydrochloric acid and then transferred after cooling; another document "Determination of boron oxide in glass by inductively coupled plasma atomic emission spectrometry with yttrium internal standard", Wan Zetao et al., Glass Fiber, No. 3, 2024, replaces the alkali with anhydrous sodium carbonate and melts it in a muffle furnace at 950℃ for 15min for post-treatment; there are also documents that use acid treatment method, such as the document "Determination of boron in glass by inductively coupled plasma atomic emission spectrometry" Wang Hong et al., Physical and Chemical Testing-Chemical Volume, 2010 In the 46th volume, issue 12 of 2017, mannitol (0.20-2.00g) + hydrofluoric acid (3-15ml) were placed in a non-boiling water bath and heated to evaporate to dryness. Hydrofluoric acid was added during the process. After the sample was dissolved, hydrochloric acid (1+1) was added to dissolve it. The sample was injected after the test solution became clear. The document "Discussion on the Determination of B2O3 Content in Glass by Inductively Coupled Plasma Emission Spectrometry", Huang Meihua, Laboratory Testing, April 2024, Volume 2, Issue 4 discussed the comparison of glass pretreatment methods, the differences between mixed acid decomposition (using nitric acid + hydrofluoric acid) and potassium hydroxide fusion method, and pointed out that there was precipitation in the test solution in the alkali fusion method. A mixed acid nitric acid (10-15 drops) plus hydrofluoric acid (5-7ml) were placed on a hot plate and heated to evaporate to dryness. The treatment was repeated once, and hydrochloric acid (1+1) solution was added to heat until dissolved before injection.

[0007] The above optimized method uses acid or alkali for high temperature heating in the pretreatment process. The existing technology has the following problems from the perspectives of operation time, convenience, safety, and method accuracy:

[0008] 1. There are many processing steps and repeated processing operations, the processing time is more than 2 hours, and the operation time is long;

[0009] 2. A large amount of acid / alkali is used, and heating is performed during the operation, which increases the risk factor of the operation;

[0010] 3. The pretreatment process is complicated, and the losses in the process and the difficulty of human operation increase, which affects the accuracy and reproducibility of the method. For example, the alkali dissolution method has the problem of incomplete dissolution of the glass frit, colloidal insoluble matter or precipitation in the solution, and a large amount of salt is introduced during the analysis process, which interferes with the detection and cannot guarantee the accuracy of the measurement. When using a mixed acid containing hydrofluoric acid for treatment, open heating is generally used, and boron (HBF4 decomposes at 130°C) loss is easily generated during the treatment process, affecting the accuracy of the analysis results, especially the measurement of glass samples with high boron content.

[0011] Therefore, it is of great significance to establish a stable, accurate and simple method for detecting the content of boron trioxide in pharmaceutical glass. 3. Summary of the invention

[0012] The purpose of the present invention is to solve the problems existing in the prior art, provide a method for detecting the content of boron trioxide in pharmaceutical glass, and establish a stable, accurate and simple method for detecting boron trioxide.

[0013] The present invention provides a method for detecting the content of boron trioxide in pharmaceutical glass, comprising:

[0014] (1) Sample preparation: Take a glass sample, break it, and place the fragments in an automatic sample grinder to obtain a sample;

[0015] (2) Preparation of sample solution: accurately weigh an appropriate amount of sample and place it in a polypropylene bottle, add hydrofluoric acid to dissolve it, dilute it to the mark with water, and shake well to obtain the sample solution;

[0016] (3) Preparation of test solution: Accurately measure the sample solution into a volumetric flask and dilute to volume with solvent to obtain the test solution;

[0017] (4) ICP-MS was used to detect the boron in the test solution.

[0018] The setting parameters of the fully automatic sample rapid grinding instrument of the present invention are: grinding frequency 55-65HZ, grinding interruption time: 0-5s, grinding operation time 60-90s, and grinding operation times 1-3 times. Preferably, the setting parameters of the fully automatic sample rapid grinding instrument are: grinding frequency 55HZ, grinding interruption time: 5s, grinding operation time 60s, and grinding operation times 3 times.

[0019] The particle size range of the sample described in the present invention is D90≤250μm, D10≤75μm.

[0020] In the preparation of the sample solution of the present invention, the amount of the sample accurately weighed is 2 to 5 mg.

[0021] The present invention adopts ICP-MS to detect the boron in the test solution, and the acquisition time is 1 to 3 seconds.

[0022] The solvent for preparing the sample solution of the present invention is water or 2% to 5% nitric acid, preferably water or 2% nitric acid.

[0023] The hydrofluoric acid solution described in the present invention is 40% hydrofluoric acid.

[0024] The method for detecting the content of boron trioxide in the medicinal glass of the present invention further comprises calculating the content of boron trioxide by using a standard curve method.

[0025] The method for detecting the content of boron trioxide in pharmaceutical glass of the present invention further comprises the preparation of a standard curve series of standard solutions and an internal standard solution, wherein the solution preparation is diluted with a 2% nitric acid solution.

[0026] In the method for detecting the content of boron trioxide in pharmaceutical glass of the present invention, the linear range of the standard curve is 0-60 ppb to 0-400 ppb. It can be understood that within the range of the standard curve, the dilution multiple of the sample solution is not limited, that is, the dilution multiple of the sample solution is arbitrarily set based on the content of boron trioxide in the sample, so that it falls within the linear range, and the preferred concentration falls near the midpoint of the linearity.

[0027] The boron trioxide content detection of the present invention is calculated using the following formula:

[0028]

[0029] In the formula, C is the measured concentration, ng / ml; V is the volume of the test solution, ml; m is the sample weight, mg; 69.92 is the relative molecular mass of boron trioxide; 10.81 is the relative atomic mass of boron.

[0030] The method for detecting the content of boron trioxide in the pharmaceutical glass of the present invention further comprises a standard curve establishment step, including:

[0031] (1) Preparation of a series of standard solutions: accurately measure 1000 μg / ml of boron standard solution, place it in a 50 ml polypropylene bottle, dilute it to the mark with 2% nitric acid solution, and shake well; accurately measure appropriate amounts of the marked concentrated solution, place it in polypropylene bottles of different volumes, dilute it to the mark with 2% nitric acid solution, and shake well to obtain the solution;

[0032] (2) Preparation of internal standard solution: Accurately measure 500 μl of scandium single element standard solution and place it in a 50 ml polypropylene bottle, dilute it to the scale with 2% nitric acid solution, and shake well; accurately measure 2.5 ml and place it in a 50 ml polypropylene bottle, dilute it to the scale with 2% nitric acid solution, and shake well.

[0033] The present invention further provides a method for detecting the content of boron trioxide in pharmaceutical glass, comprising:

[0034] (1) Preparation of a series of standard solutions: accurately measure 1000 μg / ml of boron standard solution, place it in a 50 ml polypropylene bottle, dilute it to the mark with 2% nitric acid solution, and shake well; accurately measure appropriate amounts of the marked concentrated solution, place it in polypropylene bottles of different volumes, dilute it to the mark with 2% nitric acid solution, and shake well to obtain the solution;

[0035] (2) Preparation of internal standard solution: accurately measure 500 μl of scandium single element standard solution, place it in a 50 ml polypropylene bottle, dilute it to the mark with 2% nitric acid solution, and shake well; accurately measure 2.5 ml of it, place it in a 50 ml polypropylene bottle, dilute it to the mark with 2% nitric acid solution, and shake well;

[0036] (3) Sample preparation: Take a glass sample, break it, and place the fragments in an automatic sample grinder to obtain the sample;

[0037] (4) Preparation of sample solution: accurately weigh an appropriate amount of sample and place it in a polypropylene bottle, add 1 ml of hydrofluoric acid to dissolve it, dilute it to the mark with water, and shake well to obtain the sample solution;

[0038] (5) Preparation of test solution: Accurately measure the sample solution into a volumetric flask and dilute to volume with solvent to obtain the test solution;

[0039] (6) ICP-MS was used to detect the boron in the test solution.

[0040] The present invention further provides the use of the method for detecting boron trioxide in pharmaceutical glass, including the use in the quality control of high borosilicate glass, medium borosilicate glass and low borosilicate glass. Preferably, the use in the quality control of high borosilicate glass.

[0041] The beneficial technical effects of the present invention are as follows: the detection method of the content of diboron trioxide in the pharmaceutical glass provided by the present invention, the pretreatment and detection method used in the present invention patent are simple and efficient, with high sensitivity and accuracy, no complicated pretreatment method in operation, and can achieve the purpose of on-machine detection without heating and direct dissolution, while also avoiding the loss of HBF4 that may be caused by hydrofluoric acid during the heating process, improving the accuracy of the method, and being able to quickly detect the content of diboron trioxide in type I glass. In addition, in terms of pretreatment, the present invention is simple to operate, uses a small amount of sample, and the processing time of a single sample is within 20 minutes, and has low dependence on the operator's experience; the amount of corrosive acid (HF) used during the operation is 1 ml, and there is no high-temperature equipment in the preparation process, which greatly improves safety; in the selection of detection methods, the boron content is determined by inductively coupled plasma mass spectrometry, and the instrument has high resolution, high sensitivity, low detection limit, simple operation, fast speed, and no matrix interference. 4. Specific implementation methods

[0042] Specific embodiments of the present invention are described in detail below. It should be noted that the embodiments described below are exemplary and are only used to explain the present invention, and should not be construed as limiting the present invention.

[0043] Determination of Boron Trioxide Content in Type I Glass

[0044] Solution preparation (taking the standard solution range of 0-60ppb and the test sample dilution multiple of 12500 times as an example)

[0045] Preparation of a series of standard solutions: Accurately measure 100 μl of boron single element standard solution (1000 μg / ml) and place it in a 50 ml polypropylene bottle, dilute it to the scale with 2% (2→100) nitric acid solution, and shake well; accurately measure 0, 50 μl, 150 μl, 250 μl, 500 μl, 750 μl, and 1.5 ml respectively and place them in different 50 ml polypropylene bottles, dilute it to the scale with 2% (2→100) nitric acid solution, and shake well.

[0046] Preparation of internal standard solution: Accurately measure 500 μl of scandium single element standard solution and place it in a 50 ml polypropylene bottle, dilute it to the scale with 2% (2→100) nitric acid solution, and shake well; Accurately measure 2.5 ml and place it in a 50 ml polypropylene bottle, dilute it to the scale with 2% (2→100) nitric acid solution, and shake well.

[0047] Preparation of test solution: Take 1 type I glass, break it and place the fragments in a fully automatic sample rapid grinder (operating parameters: grinding frequency 55H Z, grinding interruption time: 5s, grinding operation time 60s, grinding operation times 3 times), after crushing, accurately weigh about 5mg of the sample and place it in a 50ml polypropylene bottle, add 1ml of hydrofluoric acid to fully immerse the sample, dilute with water to the scale, and shake well; accurately measure 200μl and place it in a 50ml polypropylene bottle, dilute with 2% (2→100) nitric acid solution to the scale, shake well, and obtain.

[0048] Instrument and chromatographic conditions

[0049] Instrument: Inductively coupled plasma mass spectrometer (ICP-MS)

[0050] Instrument method: Integration time: 3s, Detection mode: He mode

[0051] Acquisition mode: Peak Pattern: 3 points, Replicates: 3, Sweeps / Replicate: 100

[0052] Determination method: The boron isotope selected for determination is 11 B 45 Sc is used as the internal standard, and the standard curve method with online internal standard real-time calibration is used for determination (the internal standard solution is introduced online by a peristaltic pump), and the 2% (2→100) nitric acid solution is used as the zero concentration sample, and the standard curve solutions of different concentrations are measured. The ratio (Ratio) of each element response value and the corresponding internal standard element response value is used as the ordinate, and the concentration is used as the abscissa to draw the standard curve. If the corresponding element is detected in the blank solution, after deducting it from the test solution, the corresponding concentration is calculated according to the standard curve method.

[0053] Example 1 Standard Curve Range Determination

[0054] (1) Determine the range of the calibration solution (0-60 ppb)

[0055] Preparation of series of standard solutions ①: Accurately measure 100 μl of boron single element standard solution (1000 μg / ml) and place it in a 50 ml polypropylene bottle, dilute it to the scale with 2% (2→100) nitric acid solution, shake well, and use it as standard solution stock solution ①; accurately measure 0, 50 μl, 150 μl, 250 μl, 500 μl, 750 μl, and 1.5 ml respectively and place them in different 50 ml polypropylene bottles, dilute it to the scale with 2% (2→100) nitric acid solution, shake well, and obtain.

[0056] Preparation of internal standard solution: Accurately measure 500 μl of scandium single element standard solution and place it in a 50 ml polypropylene bottle, dilute it to the scale with 2% (2→100) nitric acid solution, and shake well; Accurately measure 2.5 ml and place it in a 50 ml polypropylene bottle, dilute it to the scale with 2% (2→100) nitric acid solution, and shake well.

[0057] The linear results are shown in Table 1. The results show that the correlation coefficient for the determination of boron element in the range of 0 to 60 ppb is 0.9990, and the linear correlation is good.

[0058] Table 1 Linearity results 1

[0059]

[0060] (2) Determine the range of the calibration solution (0-200 ppb)

[0061] Preparation of series of standard solutions ②: Accurately measure 1 ml of boron single element standard solution (1000 μg / ml) and place it in a 50 ml polypropylene bottle, dilute it to the scale with 2% (2→100) nitric acid solution, shake well, and use it as standard solution stock solution ②; accurately measure 0, 50 μl, 150 μl, 250 μl, 500 μl, 750 μl, and 1 ml respectively and place them in different 50 ml polypropylene bottles, dilute it to the scale with 2% (2→100) nitric acid solution, shake well, and obtain.

[0062] Preparation of internal standard solution: same as above.

[0063] The linear results are shown in Table 2. The results show that the correlation coefficient for the determination of boron element in the range of 0 to 200 ppb is 0.9999, and the linear correlation is good.

[0064] Table 2 Linear results 2

[0065]

[0066] (3) Determine the range of the calibration solution (0-400 ppb)

[0067] Preparation of series of standard solutions ③: Accurately measure 1 ml of boron single element standard solution (1000 μg / ml) and place it in a 50 ml polypropylene bottle, dilute it to the scale with 2% (2→100) nitric acid solution, shake well, and use it as standard solution stock solution ③; accurately measure 0, 50 μl, 150 μl, 250 μl, 500 μl, 750 μl, and 1 ml respectively and place them in different 50 ml polypropylene bottles, dilute it to the scale with 2% (2→100) nitric acid solution, shake well, and obtain.

[0068] Preparation of internal standard solution: same as above.

[0069] The linear results are shown in Table 3. The results show that the correlation coefficient for the determination of boron element in the range of 0 to 400 ppb is 0.9999, and the linear correlation is good.

[0070] Table 3 Linearity results 3

[0071]

[0072] Example 2 Residue after injection

[0073] The "memory effect" of boron in ICP-MS instrument analysis is obvious, and it is easy for residuals to interfere with the accuracy of the test results. In order to reduce the memory effect of boron and reduce the impact of residuals on the test results, the response values ​​of blank solvents before and after the injection of the standard curve were compared with the upper limit concentration of 60ppb, 200ppb, and 400ppb, respectively, as shown in Table 4. The results show that when the upper limit of the standard curve is 60ppb, there is no significant difference in the blank response value of the instrument before and after injection, and the instrument is not easy to have residuals; when the upper limit of the standard curve is 200ppb, the blank response value of the instrument after cleaning one needle after injection is consistent with that before injection, and the instrument is not easy to have residuals; when the upper limit of the standard curve is 400ppb, the blank effect after injection is high, and there is no significant decrease after more than 6 consecutive injections, which is basically consistent with the response value before injection.

[0074] In summary, the upper limit concentration of the calibration curve should not exceed 400ppb. When the concentration is too high, the boron element is not easy to clean; the upper limit concentration of the calibration curve should not be lower than 60ppb. If the measured concentration is too low, the instrument error will increase. Therefore, the recommended linear range is 0-60ppb to 0-400ppb.

[0075] Table 4 Blank residue results

[0076]

[0077]

[0078] Example 3 Detection Limit and Quantification Limit

[0079] Take blank solvent and analyze 11 times continuously. Calculate the standard deviation (SD) of the 11 concentrations, take 3SD as the detection limit and 10SD as the quantification limit. The results are shown in Table 5. The results show that the quantification limit of boron is 2.435ng / ml, and the instrument sensitivity meets the requirements.

[0080] Table 5 Detection limit and quantification limit

[0081]

[0082] Example 4 Screening of glass crushed sample particle size

[0083] Preparation of crushed glass samples: Take one piece of type I glass from different sources, break it and place the fragments in a fully automatic sample rapid grinder (operating parameters: grinding frequency 55h Z , grinding interruption time: 5s, grinding operation time 60s, grinding operation times 3 times), after crushing, transfer the powder to a clean sealed bag for standby use.

[0084] Glass samples from four different sources were manually screened for particle size, and the results are shown in Tables 6 to 9. After the samples of the above particle sizes were prepared according to the test solution method, the solutions were all clear and met the injection requirements. Therefore, the particle size range of the sample described in the present invention is D90≤250μm, D10≤75μm.

[0085] Table 6 Particle size screening results Table-1

[0086]

[0087]

[0088] Table 7 Particle size screening results Table-2

[0089]

[0090] Table 8 Particle size screening results Table-3

[0091]

[0092] Table 9 Particle size screening results Table-4

[0093]

[0094] Example 5 Sample Preparation Solvent Screening

[0095] Sample solution preparation 1 : Take 1, break it and put the fragments into the automatic sample rapid grinder (operating parameters: grinding frequency 55H Z , grinding interruption time: 5s, grinding operation time 60s, grinding operation times 3 times), after crushing, accurately weigh about 5mg of the sample and place it in a 50ml polypropylene bottle, add 1ml of hydrofluoric acid to fully immerse the sample, dilute with water to the scale, shake well, and you are done.

[0096] Sample solution preparation 2: Take a piece of type I glass, break it and place the fragments in a fully automatic sample rapid grinder (operating parameters: grinding frequency 55H Z , grinding interruption time: 5s, grinding running time 60s, grinding running times 3 times), after crushing, accurately weigh about 5mg of the sample and place it in a 50ml polypropylene bottle, add 1ml of hydrofluoric acid to fully immerse the sample, dilute to the scale with 2% nitric acid, shake well, and you are done.

[0097] Sample solution preparation 3: Take a piece of type I glass, break it and place the fragments in a fully automatic sample rapid grinder (operating parameters: grinding frequency 55H Z, grinding interruption time: 5s, grinding running time 60s, grinding running times 3 times), after crushing, accurately weigh about 5mg of the sample and place it in a 50ml polypropylene bottle, add 1ml of hydrofluoric acid to fully immerse the sample, dilute to the scale with 5% nitric acid, shake well, and you are done.

[0098] The above sample solutions are all clear and transparent, indicating that when the selected solvent is water, 2% nitric acid to 5% nitric acid, When used in different conditions, the sample preparation requirements can be met.

[0099] Example 6 Test sample preparation time

[0100] Preparation of test solution 1 (taken from "YBB00232003 Determination of Boron Trioxide"): Take the test sample (no printing), clean it, crush it, grind it into fine powder (particles should be less than 100μm), dry it at 105-110℃ for 1 hour, and cool it in a dryer for 1 hour. Take about 0.5g of fine powder, weigh it accurately, put it into a platinum crucible (or silver crucible, nickel crucible), add 4g of anhydrous sodium carbonate (or 4g of sodium hydroxide) to melt it at 850-900℃, let it cool, wash out the molten block with hot water in a 300ml beaker, add 20ml of hydrochloric acid to decompose the molten block, and then clean the crucible with a small amount of hydrochloric acid solution (1→2), and combine the washings in the beaker. After the molten block is completely decomposed, use calcium carbonate to neutralize the remaining acid, and add 4g of calcium carbonate in excess. Put the beaker in a water bath and boil for about 3 hours. 0 minutes later, filter with qualitative quick filter paper, add a little ethylenediaminetetraacetic acid to the filtrate, boil, remove and cool, add 2 drops of 0.1% methyl red indicator, adjust the solution to neutral (bright yellow) with 0.1mol / L sodium hydroxide solution and 0.1mol / L hydrochloric acid solution, add 1ml of 0.1% phenolphthalein indicator and 2-3g of mannitol, titrate with sodium hydroxide titration solution (0.1mol / L) to a slightly reddish color, and repeat until the slightly reddish color does not fade after adding mannitol.

[0101] Test solution preparation 2 (taken from the literature "Determination of boron and other common elements in silicate glass by inductively coupled plasma emission spectrometry"): Place the sample in a nickel crucible containing 1g of potassium hydroxide, then add 2g of potassium hydroxide, melt it at low temperature first, and shake the crucible. Then continue to melt at 600-650℃ for 15-20min. Rotate the crucible so that the molten material adheres evenly to the inner wall of the crucible. Cool, and soak the molten material in a 300mL plastic cup with hot water. Cover with a watch glass, add 25mL of 50% hydrochloric acid at a time, and after the sample is completely dissolved and cooled, transfer it to a 250mL volumetric flask and shake it for testing.

[0102] Preparation of test solution 3 (taken from the document "Determination of Boron Oxide in Glass by Inductively Coupled Plasma Emission Spectrometry with Yttrium Internal Standard"): Weigh about 0.1g of sample, accurate to 0.1mg, and place in a platinum crucible. Add 2g of anhydrous sodium carbonate, mix well, and place in a muffle furnace that has been heated to 700℃, gradually heat to 950℃, melt for 15min, take out and cool, place in a quartz beaker filled with boiling water, heat on a hot plate until the melt is completely dissolved, add 25mL of 1+1 hydrochloric acid, and wash out the crucible. After cooling, transfer to a 250mL quartz volumetric flask, make up to volume and shake well (this solution is A). Take 25.00mL of A solution in a 100mL quartz volumetric flask, add 10.00mL of yttrium dilute internal standard solution and 6.5mL of 1+1 hydrochloric acid, dilute to the mark, shake well, and test.

[0103] Preparation of test solution 4 (taken from the literature "Determination of Boron in Glass by Inductively Coupled Plasma Atomic Emission Spectrometry"): Accurately weigh 0.24-0.26 g (accurate to 0.0001 g) of powder sample dried at 105-110°C in a platinum dish, moisten with a small amount of water; add 10-15 drops of nitric acid, measure 5-7 mL of hydrofluoric acid, place on a temperature-controlled hot plate (a temperature-controlled electric furnace can also be used) and evaporate to dryness, repeat the process once. Remove and wait for cooling, add 3-5 mL of hydrochloric acid (1+1) solution and appropriate amount of water, place on the temperature-controlled hot plate again to soak the residue until the residue is completely dissolved, remove and wait for cooling, transfer to a 100 mL volumetric flask and make up to volume, this is the test solution A, the solution is clear and has no precipitation, and meets the requirements for ICP-OES on-machine detection.

[0104] Table 10 Comparison of test solution preparation time

[0105] Preparation method Method 1 Method 2 Method 3 Method 4 The present invention Preparation time approx. More than 4 hours More than 2 hours 1 hour More than 2 hours Within 20 minutes

[0106] According to the preparation method and steps, the method of the present invention saves more time and has high safety.

[0107] Example 7 Sample Determination

[0108] Sample preparation: Take 1 type I glass (different sources / lots), break it and place the fragments in a fully automatic sample rapid grinder (operating parameters: grinding frequency 55h Z , grinding interruption time: 5s, grinding operation time 60s, grinding operation times 3 times), after crushing, accurately weigh about 5mg of the sample and place it in a 50ml polypropylene bottle, add 1ml of hydrofluoric acid to fully immerse the sample, dilute with water to the scale, and shake well; accurately measure 1ml and place it in a 50ml polypropylene bottle, dilute with 2% (2→100) nitric acid solution to the scale, shake well, and obtain.

[0109] The series of standard curve solutions ② / ③ and the test solution were respectively sampled and analyzed by ICP-MS. The results are shown in Table 11. Table 11 shows that the method was used to measure samples from two different manufacturers, and the results were basically consistent with the formula design values, indicating that the method has good accuracy and can accurately measure pharmaceutical glass with high boron content; the data in Table 12 show that the method has good repeatability in measuring high borosilicate glass samples from different batches from the same manufacturer.

[0110] Table 11 Differences between measured values ​​and formula values ​​of samples from different manufacturers

[0111]

[0112] Table 12 Test results of samples (high borosilicate) from different batches of the same manufacturer

[0113]

[0114]

[0115] Example 8 Spiked recovery (taking the standard solution range of 0-60 ppb and the test sample dilution multiple of 12500 times as an example)

[0116] Preparation of test solution: Take 1 type I glass, break it and place the fragments in a fully automatic sample rapid grinder (operating parameters: grinding frequency 55H Z , grinding interruption time: 5s, grinding operation time: 60s, grinding operation times 3 times), after crushing, accurately weigh about 5mg of the sample and place it in a 50ml polypropylene bottle, add 1ml of hydrofluoric acid to fully immerse the sample, dilute with water to the scale, shake well; accurately measure 200μl and place it in a 50ml polypropylene bottle, dilute with 2% (2→100) nitric acid solution to the scale, shake well, and obtain. Prepare 2 copies in parallel.

[0117] Spiked test solution: Accurately weigh about 5 mg of the crushed sample and place it in a 50 ml polypropylene bottle, add 1 ml of hydrofluoric acid to fully immerse the sample, accurately add 125 μl, 250 μl, and 375 μl (3 portions each) of boron single element standard solution, dilute to the scale with water, and shake well; Accurately measure 200 μl and place it in a 50 ml polypropylene bottle, dilute to the scale with 2% (2→100) nitric acid solution, shake well, and obtain.

[0118] Take a series of standard curve solutions ①, test solution, and spiked test solution and inject them into ICP-MS for analysis. The results are shown in Table 13. The average recovery rate of each concentration is in the range of 91.06% to 96.85%, and in the range of 80% to 120%, the RSD is 9.7%, which is less than 15%, indicating that the method has good accuracy. It should be noted that: the test selected standard curve solution ① for determination as the most demanding test condition, the determination concentration is 14 to 44 ng / ml, the determination concentration level is at the 10 ppb level, the instrument error is relatively large, the recovery rate results and RSD meet the requirements of the pharmacopoeia, indicating that the accuracy of the analytical method and pretreatment process is good.

[0119] Table 13 Recovery test results

[0120]

[0121] Note: Recovery rate (%) = (detected amount - background amount) / input amount

[0122] Detection amount (mg / g) = measured value on the machine (ng / ml) * dilution volume (ml) / sample weight (mg)

[0123] Background amount (mg / g) = background measurement value (ng / ml) * dilution volume (ml) / sample amount (mg)

[0124] Addition amount (mg / g) = spike value (ng / ml) * dilution volume (ml) / theoretical sample weight (mg)

[0125] Example 9 Repeatability test (calculated by recovery rate)

[0126] Repeatability test solution: accurately weigh about 5 mg of the crushed sample and place it in a 50 ml polypropylene bottle, add 1 ml of hydrofluoric acid to fully immerse the sample, accurately add 250 μl of boron single element standard solution, dilute to the scale with water, and shake well; accurately measure 200 μl and place it in a 50 ml polypropylene bottle, dilute to the scale with 2% (2→100) nitric acid solution, shake well, and the solution is ready. Prepare 6 portions in the same way.

[0127] The series of standard curve solutions ① and the repeated test sample solutions were injected into ICP-MS for analysis. The results are shown in Table 14.

[0128] The results showed that the same batch of samples was measured six times, and the RSD calculated by recovery was 3.36%, which was less than 15%, indicating that the repeatability of the determination method was good.

[0129] Table 14 Repeatability test results

[0130]

[0131] Note: The formula is the same as above.

Claims

1. A method for detecting the content of boron trioxide in pharmaceutical glass, characterized in that: include: (1) Sample preparation: Take a glass sample, break it, and place the fragments in an automatic sample grinder to obtain a sample; (2) Preparation of sample solution: accurately weigh an appropriate amount of sample and place it in a polypropylene bottle, add hydrofluoric acid to dissolve it, dilute it to the mark with water, and shake well to obtain the sample solution; (3) Preparation of test solution: Accurately measure the sample solution into a volumetric flask and dilute to volume with solvent to obtain the test solution; (4) ICP-MS was used to detect the boron in the test solution.

2. The method for detecting the content of boron trioxide in pharmaceutical glass according to claim 1, characterized in that: The setting parameters of the fully automatic sample rapid grinder are: grinding frequency 55-65HZ, grinding interruption time: 0-5s, grinding operation time 60-90s, and grinding operation times 1-3 times.

3. The method for detecting the content of boron trioxide in pharmaceutical glass according to claim 1, characterized in that: The particle size range of the sample is D90≤250μm, D10≤75μm.

4. The method for detecting the content of boron trioxide in pharmaceutical glass according to claim 1, characterized in that: The amount of the sample accurately weighed is 2 to 5 mg.

5. The method for detecting the content of boron trioxide in pharmaceutical glass according to claim 1, characterized in that: The acquisition time for detecting boron in the test solution by ICP-MS is 1 to 3 seconds.

6. The method for detecting the content of boron trioxide in pharmaceutical glass according to claim 1, characterized in that: The solvent used in the preparation of the sample solution is water or 2% to 5% nitric acid.

7. The method for detecting the content of boron trioxide in pharmaceutical glass according to claim 6, characterized in that: The solvent is water and 2% nitric acid.

8. The method for detecting the content of boron trioxide in pharmaceutical glass according to claim 1, characterized in that: The method further comprises the preparation of a series of standard solutions and an internal standard solution for a standard curve, wherein the solution is prepared by diluting with a 2% nitric acid solution.

9. The method for detecting the content of boron trioxide in pharmaceutical glass according to claim 1, characterized in that: The method further comprises using a standard curve method to calculate the content of diboron trioxide; using the following formula to calculate: In the formula, C is the measured concentration, ng / ml; V is the volume of the test solution, ml; m is the sample weight, mg; 69.92 is the relative molecular mass of boron trioxide; 10.81 is the relative atomic mass of boron.

10. A method for detecting boron trioxide in medicinal glass, characterized in that: The method is used in quality control of high borosilicate glass, medium borosilicate glass and low borosilicate glass.

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