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CN-122017058-A - Method for detecting methanol content in liquid essence

CN122017058ACN 122017058 ACN122017058 ACN 122017058ACN-122017058-A

Abstract

The application provides a method for detecting the content of methanol in liquid essence, and belongs to the field of medicine analysis. The application adopts a capillary column method, takes dimethylpolysiloxane as a stationary phase, carries out headspace sampling, and calculates the content of methanol according to an external standard method by using peak area. Compared with the prior art, the method has the advantages of strong specificity, good reproducibility, high sensitivity and the like.

Inventors

  • CHEN YING
  • PENG PENG
  • LI AO
  • ZHAO QIHANG
  • LI YING

Assignees

  • 东北制药集团沈阳第一制药有限公司

Dates

Publication Date
20260512
Application Date
20251219

Claims (10)

  1. 1. The method for detecting the methanol content in the liquid essence is characterized by adopting a capillary column method and comprising the following steps of: (1) Chromatographic conditions Chromatographic column, taking dimethyl polysiloxane as stationary phase; the column temperature is that the initial column temperature is 30-60 ℃ and is maintained for 3-9 minutes, and then the temperature is increased to 170-190 ℃ at the rate of 15-25 ℃ per minute and is maintained for 2-5 minutes; The temperature of the sample inlet is 190-240 ℃; The detector is a hydrogen flame ionization detector, and the temperature of the detector is 280-350 ℃; (2) Preparation of control solution (3) Preparation of test solutions (4) Measurement method Taking the sample solution and the control solution to be tested, respectively taking headspace samples, recording a chromatogram, wherein the chromatographic peak separation degree of methanol and the adjacent solvent is greater than 1.5, and calculating according to an external standard method and the peak area.
  2. 2. The method for detecting the methanol content in the liquid essence according to claim 1, wherein the chromatographic conditions further comprise: The carrier gas is nitrogen, and the flow rate is 3-5 ml/min; the split ratio is 20:1-50:1; the balance temperature of the headspace bottle is 80-90 ℃, the balance time is 15-25 minutes, and the temperature of the transmission line is 85-115 ℃.
  3. 3. The method for detecting the methanol content in the liquid essence according to claim 1, wherein the chromatographic column uses 100% dimethylpolysiloxane as a stationary phase, the chromatographic column is selected from one of DM-1, DB-1, SPB-1, HP-1, BP-1 and 007-1, the specification of the chromatographic column is selected from 45-160 m multiplied by 0.5-0.6 mm multiplied by 4.5-5.5 mu m, and preferably, the specification of the chromatographic column is selected from 45-65 m multiplied by 0.5-0.6 mm multiplied by 4.5-5.5 mu m.
  4. 4. A method for detecting the methanol content of a liquid flavor according to claim 3, wherein the specification of the column is selected from the group consisting of "50m×0.53mm×5 μm", "60m×0.53mm×5 μm".
  5. 5. The method for detecting the methanol content in the liquid essence according to claim 1, wherein the preparation method of the control solution is characterized in that 2-3 ml of methanol is precisely measured and placed in a 100ml measuring flask, water is added for dilution to a scale, shaking is carried out, 3-5 ml of the solution is precisely measured and placed in a 50ml volumetric flask, 50-70% ethanol solution is used for dilution to the scale, shaking is carried out, 2-5 ml of the solution is precisely measured and placed in a 10ml headspace bottle, and sealing is carried out; the preparation method of the sample solution comprises the steps of precisely measuring 2-4 ml of the sample, placing the sample in a10 ml headspace bottle, and sealing to obtain the sample solution.
  6. 6. The method for detecting the methanol content in the liquid essence, which is disclosed in claim 5, is characterized in that the control solution is prepared by precisely measuring 2.5ml of methanol in a 100ml measuring flask, adding water for dilution to a scale, shaking up, precisely measuring 4ml of the solution in a 50ml volumetric flask, diluting to the scale with 60% ethanol solution, shaking up, precisely measuring 3ml of the solution in a 10ml headspace bottle, and sealing, wherein the sample solution is prepared by precisely measuring 3ml of the sample in the 10ml headspace bottle, sealing, and is used as the sample solution, wherein the sample is selected from liquid essence, and the liquid essence is selected from one of orange-flavor liquid essence, lemon-flavor liquid essence and banana-flavor liquid essence.
  7. 7. The method for detecting the methanol content in the liquid essence according to claim 2, wherein the method comprises the following steps: (1) Chromatographic conditions The chromatographic column takes 100% dimethyl polysiloxane as a stationary phase, and the specification of the chromatographic column is selected from 49-61 m multiplied by 0.50-0.55 mm multiplied by 4.5-5.5 mu m; the column temperature is that the initial column temperature is 35-45 ℃ and is maintained for 5-7 minutes, then the temperature is raised to 175-185 ℃ at the rate of 17-22 ℃ per minute and is maintained for 2-4 minutes; the temperature of the sample inlet is 190-220 ℃; The detector is a hydrogen flame ionization detector, and the temperature of the detector is 280-330 ℃; the carrier gas is nitrogen, and the flow rate is 3.5-4.5 ml/min; the split ratio is 25:1-35:1; The balance temperature of the headspace bottle is 80-90 ℃, the balance time is 15-25 minutes, and the temperature of a transmission line is 90-110 ℃; (2) Precisely weighing 2-3 ml of methanol, placing in a 100ml measuring flask, adding water for dilution to a scale, shaking uniformly, precisely weighing 3-5 ml of the solution, placing in a 50ml volumetric flask, diluting to the scale with 50-70% ethanol solution, shaking uniformly, precisely weighing 2-4 ml, placing in a 10ml headspace bottle, and sealing; (3) Precisely measuring 2-4 ml of the sample solution, placing the sample solution in a 10ml headspace bottle, and sealing to obtain the sample solution; (4) Measurement method Taking the sample solution and the control solution to be tested, respectively taking headspace samples, recording a chromatogram, wherein the chromatographic peak separation degree of methanol and the adjacent solvent is greater than 1.5, and calculating according to an external standard method and the peak area.
  8. 8. The method for detecting the methanol content in the liquid essence according to claim 2, wherein the method comprises the following steps: (1) Chromatographic conditions Chromatography column DM-1,50m 0.53mm 5 μm; The column temperature is 40 ℃ at the beginning and is maintained for 6 minutes, and then the temperature is increased to 180 ℃ at the rate of 20 ℃ per minute and is maintained for 3 minutes; the temperature of the sample inlet is 200 ℃; a detector, namely a hydrogen flame ionization detector, wherein the temperature of the detector is 300 ℃; carrier gas, nitrogen, flow rate of 4 ml/min; the split ratio is 30:1; the balance temperature of the headspace bottle is 85 ℃, the balance time is 20 minutes, and the temperature of a transmission line is 100 ℃; (2) Precisely weighing 2.5ml of methanol, placing in a 100ml measuring flask, adding water for dilution to a scale, shaking uniformly, precisely weighing 4ml of the solution, placing in a 50ml volumetric flask, diluting to the scale with 60% ethanol solution, shaking uniformly, precisely weighing 3ml, placing in a 10ml headspace bottle, and sealing; (3) Precisely measuring 3ml of the sample solution, placing in a 10ml headspace bottle, and sealing to obtain the sample solution; (4) Measurement method Taking the sample solution and the control solution to be tested, respectively taking headspace samples, recording a chromatogram, wherein the chromatographic peak separation degree of methanol and the adjacent solvent is greater than 1.5, and calculating according to an external standard method and the peak area.
  9. 9. The method for detecting the content of methanol in liquid essence according to claim 1, wherein the quantitative limit of methanol is 2.3 mug/ml and the detection limit of methanol is 0.7 mug/ml.
  10. 10. The method for detecting the methanol content in the liquid essence according to claim 1, wherein the formula for calculating the methanol content by the peak area according to the external standard method is as follows: wherein: A Feed device the peak area of methanol in the sample solution; p purity of control,%; a For a pair of area of methanol peak in control solution.

Description

Method for detecting methanol content in liquid essence Technical Field The invention relates to a method for detecting the content of methanol in liquid essence in the field of pharmaceutical analysis. Background The liquid essence is an auxiliary material used by various oral solution products in the pharmaceutical field, such as levocarnitine oral solution, paracetamol pseudoephedrine oral solution and the like. Because of the reasons of technology and the like, the liquid essence has methanol residues, and the methanol has accumulation effect in the body and mainly damages the optic nerve, so that a small amount of methanol can also cause chronic poisoning, and symptoms are headache, nausea, blurred vision, blindness and the like. The requirement of the Chinese pharmacopoeia (2025 edition) on the residual amount of methanol is controlled, at present, the detection and execution standard of the methanol content in the liquid essence is GB/T7917.4-1987, a gas chromatography is adopted, and a chromatographic column adopts a packed column (a glass column or a stainless steel column with the specification of 2m multiplied by phi 4 mm) and is internally filled with GDX-102 (60-80 meshes) carriers. The separation degree of each chromatographic peak in the Chinese pharmacopoeia (four 2025 edition) is required to be more than 1.5, the chromatographic column efficiency of the method is low, the separation degree of methanol peak and other peaks can not be more than 1.5, the implementation standard GB/T7917.4-1987 is old, the updating is not carried out until now, and the filling column is rarely used at present. Therefore, the method for detecting the methanol content in the liquid essence has the advantages of strong specificity, good reproducibility, high sensitivity, simple operation, wide application of detection equipment and instruments and low detection cost, and is a new topic to be solved urgently at present. Disclosure of Invention The invention mainly aims to provide a method for detecting the methanol content in liquid essence, which adopts a gas chromatography method and uses dimethylpolysiloxane as a stationary phase for detection, and has the advantages of strong specificity, good reproducibility, high sensitivity, simple operation, wide application of detection equipment and instruments, low detection cost and the like. The invention aims to realize the method for detecting the methanol content in the liquid essence, which adopts a capillary column method and comprises the following steps: (1) Chromatographic conditions Chromatographic column, taking dimethyl polysiloxane as stationary phase; the column temperature is that the initial column temperature is 30-60 ℃ and is maintained for 3-9 minutes, and then the temperature is increased to 170-190 ℃ at the rate of 15-25 ℃ per minute and is maintained for 2-5 minutes; The temperature of the sample inlet is 190-240 ℃; The detector is a hydrogen flame ionization detector, and the temperature of the detector is 280-350 ℃; (2) Preparation of control solution (3) Preparation of test solutions (4) Measurement method Taking the sample solution and the control solution to be tested, respectively taking headspace samples, recording a chromatogram, wherein the chromatographic peak separation degree of methanol and the adjacent solvent is greater than 1.5, and calculating according to an external standard method and the peak area. The chromatographic conditions further include: The carrier gas is nitrogen, and the flow rate is 3-5 ml/min; the split ratio is 20:1-50:1; the balance temperature of the headspace bottle is 80-90 ℃, the balance time is 15-25 minutes, and the temperature of the transmission line is 85-115 ℃. The chromatographic column takes 100% dimethylpolysiloxane as a stationary phase, the chromatographic column is selected from one of DM-1, DB-1, SPB-1, HP-1, BP-1 and 007-1, the specification of the chromatographic column is selected from 45-160 m multiplied by 0.5-0.6 mm multiplied by 4.5-5.5 mu m, and preferably, the specification of the chromatographic column is selected from 45-65 m multiplied by 0.5-0.6 mm multiplied by 4.5-5.5 mu m. The specification of the chromatographic column is selected from one of "50m×0.53mm×5 μm", "60m×0.53mm×5 μm". The preparation method of the control solution comprises the steps of precisely measuring 2-3 ml of methanol, placing in a 100ml measuring flask, adding water for dilution to a scale, shaking uniformly, precisely measuring 3-5 ml of the solution, placing in a 50ml volumetric flask, diluting to the scale with 50-70% ethanol solution, shaking uniformly, precisely measuring 2-5 ml of the solution, placing in a 10ml headspace bottle, and sealing; the preparation method of the sample solution comprises the steps of precisely measuring 2-4 ml of the sample, placing the sample in a10 ml headspace bottle, and sealing to obtain the sample solution. The preparation method of the control solution comprises the step