Method for determining content of ethanol in ferrous succinate tablet
By using gas chromatography combined with headspace injection and specific diluent in the detection of ferrous succinate tablets, the interference problem of ethanol detection in the injection solution is solved, and the detection results with high sensitivity and accuracy are achieved, ensuring that Safety of drug quality.
Patent Information
- Application Number
- CN202411732113.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-29
- Publication Date
- 2025-02-14
AI Technical Summary
The prior art is difficult to accurately detect the residual ethanol in ferrous succinate tablets. Especially when the injection solution contains a large amount of water and inorganic salts, the ethanol output will be disturbed, resulting in inaccurate detection results.
Using gas chromatography combined with headspace injection and specific diluents (such as 50% dimethylformamide), set up a capillary column with 6% cyanopropylphenyl-94% dimethylpolysiloxane as the fixing solution. Appropriate heating procedures and detection conditions to reduce solvent interference and improve detection sensitivity.
Accurate detection of ethanol in ferrous succinate tablets is achieved, solvent interference is reduced, detection sensitivity and accuracy is improved, and drug quality is ensured.
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Abstract
Description
Technical Field
[0001] The invention relates to a method for determining residual ethanol in a ferrous succinate tablet, in particular to detecting ethanol in the ferrous succinate tablet by utilizing a gas chromatography method, and belongs to the technical field of analytical chemistry. Background Art
[0002] Ferrous succinate tablets are used to prevent and treat iron deficiency anemia. Iron is a component of hemoglobin in red blood cells. When iron is deficient, the amount of hemoglobin synthesized by red blood cells decreases, causing the red blood cells to become smaller and their oxygen-carrying capacity to decrease, resulting in iron deficiency anemia. Oral administration of this product can supplement iron and correct iron deficiency anemia.
[0003] Ferrous succinate mainly contains ferrous iron, and its main function is to supplement iron. Ferrous iron enters the body and is converted into ferric iron, which finally participates in the metabolism of iron in the body and is used to synthesize red blood cells. Its main function is to supplement the raw materials for hematopoiesis and treat iron deficiency anemia. Figure 1 It is the chemical structural formula of ferrous succinate.
[0004] Ethanol is used in the production process of ferrous succinate, and we intend to study and control the ethanol content in ferrous succinate tablets.
[0005] Ethanol is tested under residual solvents.
[0006] Ethanol is listed as a Class III residual solvent in Part IV of the 2020 edition of the Chinese Pharmacopoeia and must be controlled below 0.5%.
[0007] Ethanol, also known as alcohol, is harmful to the human body in many ways. It mainly damages the liver, the digestive system, the nervous system, and the cardiovascular system. At the same time, ethanol can irritate the gastric mucosa, leading to increased gastric acid secretion, which can cause gastritis, gastric ulcers and other diseases. The impact on the nervous system is manifested in slow brain activity, leading to symptoms such as memory loss and lack of concentration. In addition, ethanol can also affect the normal function of the intestines, leading to symptoms such as diarrhea and abdominal pain.
[0008] In order to strictly control the quality of drugs and ensure the safety of clinical drug use, it is necessary to control the ethanol in ferrous succinate tablets.
[0009] Compared with the raw material of ferrous succinate, the injection contains a large amount of water, inorganic salts, etc. These components will cause certain damage to the gas phase detection capillary column, and water as a solvent will interfere with the elution of ethanol. Therefore, it is necessary to develop a method for the determination of ethanol in injections, which is a technical problem that needs to be solved urgently. Summary of the invention
[0010] The purpose of the present invention is to establish a method for determining residual ethanol in ferrous succinate tablets. The method can accurately detect the ethanol in the ferrous succinate tablets, which is beneficial to ensuring the quality safety of the ferrous succinate tablets.
[0011] The method for detecting ethanol in ferrous succinate tablets disclosed by the present invention comprises the following steps: using a capillary column with 6% cyanopropylphenyl-94% dimethylpolysiloxane (or a similar polarity) as a stationary liquid as a chromatographic column, using nitrogen as a carrier gas, starting with a column temperature of 40°C, maintaining for 5 minutes, heating to 200°C at a rate of 20°C per minute, and maintaining for 5 minutes; and performing sample analysis by headspace injection, with an injection port temperature of 200°C and a detector temperature of 250°C.
[0012] The headspace equilibrium temperature is 60-90° C. and the equilibrium time is 20-40 minutes; more preferably, the equilibrium temperature is 80° C. and the equilibrium time is 30 minutes.
[0013] The injection volume is 0.5 ml to 2.0 ml, and more preferably 1.0 ml.
[0014] The chromatographic column is a capillary column with 6% cyanopropylphenyl-94% dimethylpolysiloxane (or similar polarity) as the stationary liquid; more preferably, it is DB-624 (30m*0.32μm*1.8mm).
[0015] The diluent used for the injection solution can be water or 50% dimethylformamide, preferably 50% dimethylformamide.
[0016] The concentration of the test sample is 10 mg / ml to 100 mg / ml, preferably 50 mg / ml.
[0017] The present invention has the positive effects that: the method adopts the headspace sampling mode and adopts an organic solvent as a diluent, thereby reducing the interference of the solvent on ethanol; and the method has high sensitivity, thereby ensuring the safety and effectiveness of the quality of the ferrous succinate tablets. BRIEF DESCRIPTION OF THE DRAWINGS
[0018] Figure 1 is the chemical structural formula of ferrous succinate; Figure 2 is the chromatogram of blank solvent; Figure 3 is the chromatogram of ethanol reference solution; Figure 4 is the chromatogram of the test solution; DETAILED DESCRIPTION
[0019] The present invention will be further described below in conjunction with specific embodiments, and the advantages and features of the present invention will become clearer as the description proceeds. However, the embodiments are merely exemplary and do not constitute any limitation to the scope of the present invention.
[0020] Example 1 A method for detecting ethanol in ferrous succinate tablets comprises the following steps: Solvent: Water.
[0021] Solution preparation: Step 1: Reference solution: Accurately weigh 250 mg of ethanol, place it in a 10 ml volumetric flask, add solvent to dilute to the scale, and shake well; Accurately measure 1 ml, place it in a 10 ml volumetric flask, add solvent to dilute to the scale, and shake well as the reference stock solution.
[0022] Step 2: Accurately measure 2 ml of the reference stock solution, place it in a 20 ml headspace bottle, and shake well to use as the reference solution.
[0023] Step 3: Accurately weigh 100 mg of the test sample (10 ferrous succinate tablets ground into powder), place it in a 20 ml headspace bottle, add 2 ml of solvent, mix well, and use it as the test sample solution.
[0024] Prepare 2 more solutions in parallel in step 3 Step 4: Accurately weigh 100 mg of the test sample (10 pieces of ferrous succinate ground into powder), place it in a 20 ml headspace bottle, add 2 ml of the reference solution, mix well, and use it as the spiked test solution.
[0025] Prepare 6 portions of the above step 4 solution in parallel Chromatographic conditions: Agilent gas chromatograph.
[0026] The chromatographic column is DB-624 (30m*0.32μm*1.8mm).
[0027] Heating program: start at 40°C, maintain for 5 minutes, increase the temperature to 200°C at a rate of 20°C per minute, and maintain for 5 minutes.
[0028] The injection port temperature was 200 °C.
[0029] The detector temperature was 250°C.
[0030] The headspace vial equilibrium temperature was 80°C.
[0031] The equilibration time was 30 minutes.
[0032] The injection volume is 1 ml result: Residual Solvents Test solution Spiked test solution Ethanol Detection amount (%) Recovery rate (%) Measurement results Not detected 83.21 Example
[0033] A method for detecting ethanol in ferrous succinate tablets comprises the following steps: Solvent: 50% dimethylformamide.
[0034] Solution preparation: Step 1: Reference solution: Accurately weigh 250 mg of ethanol, place it in a 10 mL volumetric flask, add solvent to dilute to the scale, and shake well; accurately measure 1 mL, place it in a 10 mL volumetric flask, add solvent to dilute to the scale as the reference stock solution.
[0035] Step 2: Accurately measure 2 ml of the reference stock solution, place it in a 20 ml headspace bottle, add 2 ml of solvent, shake, and mix to obtain the reference solution.
[0036] Step 3: Accurately weigh 100 mg of the test sample (10 ferrous succinate tablets ground into powder), place it in a 20 ml headspace bottle, add 2 ml of solvent, mix well, and use it as the test sample solution.
[0037] Prepare 2 more solutions in parallel in step 3 Step 4: Accurately weigh 100 mg of the test sample (10 ferrous succinate tablets ground into powder), place it in a 20 ml headspace bottle, add 2 ml of the reference stock solution, mix well, and use this as the spiked test solution.
[0038] Prepare 6 portions of the above step 4 solution in parallel Chromatographic conditions: Agilent gas chromatograph.
[0039] The chromatographic column is DB-624 (30m*0.32μm*1.8mm).
[0040] Heating program: start at 40°C, maintain for 5 minutes, increase the temperature to 200°C at a rate of 20°C per minute, and maintain for 5 minutes.
[0041] The injection port temperature was 200 °C.
[0042] The detector temperature was 230°C.
[0043] The headspace vial equilibrium temperature was 80°C.
[0044] The equilibration time was 25 minutes.
[0045] The injection volume is 1 ml result: Residual Solvents Test solution Spiked test solution Ethanol Detection amount (%) Recovery rate (%) Measurement results Not detected 115.84
Claims
1. A method for determining residual ethanol in ferrous succinate tablets, characterized in that: Ethanol was determined by gas chromatography, specifically, a capillary column with 6% cyanopropylphenyl-94% dimethylpolysiloxane (or similar polarity) as the stationary phase was used as the chromatographic column, nitrogen was used as the carrier gas, the initial column temperature was 40°C, maintained for 5 minutes, and then increased to 200°C at a rate of 20°C per minute and maintained for 5 minutes; headspace injection was used, and a high-boiling point organic solvent was used to dilute the ferrous succinate tablets to prepare the test sample.
2. The headspace chromatography according to claim 1, characterized in that: The headspace conditions are described as an equilibrium temperature of 60-90°C and an equilibrium time of 20-40 minutes.
3. The organic solvent according to claim 1, characterized in that: The organic solvents described can be water and 50% dimethylformamide respectively.
4. The test solution preparation according to claim 1, characterized in that: The concentration of the test sample is 10 mg / ml~100 mg / ml.
5. The headspace condition according to claim 2, characterized in that: The conditions described are headspace equilibrium conditions, the equilibrium temperature is 80°C, and the equilibrium time is 30 minutes.