CN111686072B - Linezolid injection and preparation method thereof - Google Patents
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Abstract
The invention provides a linezolid injection and a preparation method thereof. The preparation method of the linezolid injection comprises the steps of weighing, preparing, filtering, encapsulating and sterilizing, wherein in the step of preparing and/or encapsulating, nitrogen is filled into a liquid medicine for protection. The nitrogen filling protection is carried out on the liquid medicine in the preparation and/or encapsulation steps, so that the content of 3-fluoro-4- (4-morpholinyl) aniline in a linezolid injection product can be obviously reduced, the product quality and the medication safety of the linezolid injection are favorably improved, and the medication risk of the linezolid injection is also obviously reduced due to the reduction of the content of genotoxic impurities.
Description
Technical Field
The invention relates to the field of pharmacy, and in particular relates to a linezolid injection and a preparation method thereof.
Background
Linezolid (Linezolid) having the molecular formula C16H20FN3O4The chemical name is (S) -N [ [3- [ 3-fluoro-4- (4-morpholinyl) phenyl group]-2-oxo-5-oxazolidinyl]Methyl radical]-acetamide, of the formula:
linezolid is an artificially synthesized oxazolidinone antibiotic, approved by the FDA in the united states in 2000, and is used to treat infections caused by gram-positive (G +) cocci, including suspected or confirmed nosocomial pneumonia (HAP), community-acquired pneumonia (CAP), complex skin or Skin Soft Tissue Infections (SSTI), and vancomycin-resistant enterococci (VRE) infections caused by MRSA. Linezolid is mainly administered orally or by injection, and at present, linezolid tablets, linezolid injection and the like are related products. Linezolid injection is colorless to light brown clear liquid and is prepared by adding a pH value regulator, an osmotic pressure regulator and water for injection into linezolid, wherein the main related impurities in the quality control of the linezolid injection comprise N- [ [3- [ 3-fluoro-4- (4-morpholinyl) phenyl ] amino ] -2- (R) -hydroxypropyl ] acetamide (impurity A) and N- [ 3-amino-2 (S) -hydroxypropyl ] -N- [ [ 3-fluoro-4- (4-morpholinyl) ] phenyl ] acetamide (impurity B) and the like. In addition, the linezolid injection also contains a trace amount of 3-fluoro-4- (4-morpholinyl) aniline, and the chemical structural formula is as follows:
3-fluoro-4- (4-morpholinyl) aniline is an impurity with genotoxicity, and can affect the product quality and the medication safety of linezolid injection. At present, no method for reducing the content of 3-fluoro-4- (4-morpholinyl) aniline in linezolid injection to improve the product quality and the medication safety of linezolid injection is provided.
Disclosure of Invention
Therefore, the technical problem to be solved by the invention is to reduce the content of 3-fluoro-4- (4-morpholinyl) aniline in linezolid injection to improve the product quality and the medication safety of linezolid injection, thereby providing linezolid injection and a preparation method thereof.
In a first aspect, the invention provides a preparation method of linezolid injection, which comprises the steps of weighing, preparing, filtering, encapsulating and sterilizing, wherein in the step of preparing and/or encapsulating, nitrogen is filled into a liquid medicine for protection.
Further, in the step of formulating, comprising: nitrogen is filled under the liquid surface of the water for injection and the prepared liquid medicine.
Further, in the step of formulating, comprising: adding part of prescription amount of injection water, filling nitrogen below the liquid surface, preparing liquid medicine when the dissolved oxygen in the injection water is less than 2ppm, and continuously filling nitrogen below the liquid surface in the preparation process, wherein the nitrogen pressure is 0.3-0.6 MPa.
Further, in the step of potting, comprising: filling liquid medicine, filling nitrogen on the liquid surface and sealing.
Further, in the step of encapsulating, nitrogen gas pressure is 0.1-0.6 MPa, and nitrogen is filled on the liquid surface until the headspace oxygen content is less than 1% (the headspace oxygen content is the volume percentage of oxygen in the headspace air).
Further, in the step of formulating, comprising:
adding water for injection to 90% of the total amount, adding the prescription amount of raw materials and adjuvants to dissolve completely, adding water for injection to the total amount, mixing well,
wherein the temperature of the water for injection and the liquid medicine is kept between 60 and 65 ℃ in the preparation process.
Further, in the step of filtering, comprising: in the step of filtering, comprising: sequentially carrying out primary filtration on the prepared liquid medicine through a first filter element and carrying out post-filtration through a second filter element, wherein the first filter element adopts a polyether sulfone filter element with the aperture of 0.45 mu m, and the second filter element adopts a polyether sulfone filter element with the aperture of 0.22 mu m;
in the sterilization step, the sterilization temperature is 121 ℃ and the sterilization time is 15 min.
Further, the linezolid injection comprises the following raw materials in parts by weight: linezolid, a pH regulator, an osmotic pressure regulator and water for injection.
Further, the linezolid injection comprises the following components in percentage by volume based on the total volume of the linezolid injection: 2mg/mL of linezolid, 1.92mg/mL of anhydrous citric acid, 0.76mg/mL of sodium hydroxide, 9mg/mL of sodium chloride and the balance of water for injection.
In a second aspect, the invention provides a linezolid injection prepared by the preparation method.
The technical scheme of the invention has the following advantages:
the preparation method of linezolid injection provided by the invention comprises the steps of weighing, preparing, filtering, encapsulating and sterilizing, wherein in the step of preparing and/or encapsulating, nitrogen is filled into the liquid medicine for protection. The applicant creatively discovers that the content of 3-fluoro-4- (4-morpholinyl) aniline in a linezolid injection product can be obviously reduced by performing nitrogen charging protection on a liquid medicine in the steps of preparation and/or encapsulation, so that the product quality and the medication safety of the linezolid injection are improved, and the medication risk of the linezolid injection is obviously reduced due to the reduction of the content of genotoxic impurities.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings can be obtained by those skilled in the art without creative efforts.
FIG. 1 is a standard curve for linezolid injection impurity 3 detection;
FIG. 2 is a MRM profile of a control solution of impurity 3 (4 ng/mL);
FIG. 3 is a MRM profile measured for impurity 3 in the self-made formulation of example 1;
FIG. 4 is a MRM profile measured for impurity 3 in the self-made preparation of example 2;
FIG. 5 is a MRM profile measured for impurity 3 from the home-made formulation of example 3;
FIG. 6 is the MRM profile of the assay for impurity 3 from the home-made formulation of example 4;
FIG. 7 is a MRM profile of the detection of impurity 3 of the comparative formulation;
figure 8 is a MRM profile of reference formulation impurity 3 detection.
Detailed Description
The following examples are provided to further understand the present invention, not to limit the scope of the present invention, but to provide the best mode, not to limit the content and the protection scope of the present invention, and any product similar or similar to the present invention, which is obtained by combining the present invention with other prior art features, falls within the protection scope of the present invention.
The information of materials, consumables and equipment, and the information of reference preparations and reference substances in examples and experimental examples are shown in tables 1 to 3.
TABLE 1 materials information
TABLE 2 consumables and Equipment information
TABLE 3 reference formulation and control information
The examples do not show the specific experimental steps or conditions, and can be performed according to the conventional experimental steps described in the literature in the field. The materials, consumables and equipment used are all conventional products which can be obtained commercially, including but not limited to the materials, consumables and equipment used in the embodiments of the present application.
Example 1
Linezolid injection is prepared as follows:
the preparation method of the linezolid injection comprises the following steps:
(1) washing a rubber plug: cleaning the rubber plug by using a full-automatic rubber plug cleaning machine;
(2) weighing: weighing the linezolid, anhydrous citric acid, sodium hydroxide and sodium chloride according to the prescription amount respectively;
(3) preparation: adding water for injection into a concentration tank to 90% of the total amount, controlling the temperature at 60-65 deg.C, charging nitrogen into the liquid level (i.e. nitrogen gas input port is positioned below the liquid level to charge nitrogen gas into the liquid), the nitrogen gas pressure is 0.3MPa, detecting that when the dissolved oxygen amount in the water for injection is less than 2ppm, adding weighed anhydrous citric acid and sodium hydroxide into the concentration tank, stirring to completely dissolve, adding weighed linezolid, stirring to completely dissolve, adding weighed sodium chloride, stirring to completely dissolve, keeping the temperature of the liquid medicine at 60-65 deg.C in the preparation process, continuously charging nitrogen into the liquid level in the preparation process, the nitrogen gas pressure is 0.3MPa, transferring the liquid medicine into a dilution tank, supplementing water for injection to the total amount, stirring to be uniform, charging nitrogen into the dilution tank under the liquid level in the same way in the preparation process, the nitrogen gas pressure is 0.3MPa, finishing the preparation, detecting the pH value of the liquid medicine to be 4.8;
(4) and (3) filtering: a. primary filtration: the liquid medicine is primarily filtered by a first filter element (a polyether sulfone filter element, the aperture is 0.45 mu m, and the length is 10 inches); b. and (3) post-stage filtration: the liquid medicine is post-filtered by a second filter element (a polyether sulfone filter element, the aperture is 0.22 mu m, and the length is 10 inches);
(5) bottle washing and filling and sealing: washing and filling are carried out simultaneously, a washing machine is used for washing the borosilicate infusion bottle, and the washed infusion bottle is a thin layer without surface stains, flow marks and matt when being checked by eyes; filling the filtered liquid medicine into an infusion bottle by using a filling and nitrogen-filling corker, filling 300mL (the detection qualified standard is 300 plus 310mL) into each bottle, filling nitrogen into the bottle mouth, wherein the nitrogen pressure is 0.1MPa, and when the headspace oxygen content is detected to be less than 1%, adding a rubber plug and rolling an aluminum cap by using a capping machine;
(6) and (3) sterilization: sterilizing with a water bath sterilizer at 121 deg.C for 15 min;
(7) quality inspection: performing light inspection to remove unqualified products (glass, fiber, white blocks and other visible foreign matters, a small amount of the foreign matters, excessive amount of the foreign matters) and cracked bottles;
(8) labeling: labeling qualified products by using a linear labeling machine;
(9) and (6) packaging.
Example 2
The formula of linezolid injection is the same as that in example 1, and the preparation method of the linezolid injection comprises the following steps:
(1) washing a rubber plug: cleaning the rubber plug by using a full-automatic rubber plug cleaning machine;
(2) weighing: weighing the linezolid, anhydrous citric acid, sodium hydroxide and sodium chloride according to the prescription amount respectively;
(3) preparation: adding injection water into a concentration tank to 90% of the total amount, controlling the temperature to be 60-65 ℃, filling nitrogen under the liquid surface, wherein the nitrogen pressure is 0.3MPa, putting weighed anhydrous citric acid and sodium hydroxide into the concentration tank when the dissolved oxygen amount in the injection water is detected to be less than 2ppm, stirring to completely dissolve the anhydrous citric acid and the sodium hydroxide, adding weighed linezolid, stirring to completely dissolve the linezolid, adding weighed sodium chloride, stirring to completely dissolve the sodium chloride, keeping the temperature of the liquid medicine to be 60-65 ℃ in the preparation process, continuously filling nitrogen under the liquid surface in the preparation process, wherein the nitrogen pressure is 0.3MPa, transferring the liquid medicine to a dilution tank, supplementing the injection water to the total amount, stirring to be uniform, filling nitrogen under the liquid surface in the dilution tank in the process, wherein the nitrogen pressure is 0.3MPa, finishing the preparation, and detecting the pH value of the liquid medicine to be 4.8;
(4) and (3) filtering: a. primary filtration: the liquid medicine is primarily filtered by a first filter element (a polyether sulfone filter element, the aperture is 0.45 mu m, and the length is 10 inches); b. and (3) post-stage filtration: the liquid medicine is post-filtered by a second filter element (a polyether sulfone filter element, the aperture is 0.22 mu m, and the length is 10 inches);
(5) bottle washing and filling and sealing: washing and filling are carried out simultaneously, a washing machine is used for washing the borosilicate infusion bottle, and the washed infusion bottle is a thin layer without surface stains, flow marks and matt when being checked by eyes; filling the filtered liquid medicine into infusion bottles by using a filling nitrogen-filled corker, filling 300mL (the detection qualified standard is 300-;
(6) and (3) sterilization: sterilizing with a water bath sterilizer at 121 deg.C for 15 min;
(7) quality inspection: performing light inspection to remove unqualified products (glass, fiber, white blocks and other visible foreign matters, a small amount of the foreign matters, excessive amount of the foreign matters) and cracked bottles;
(8) labeling: labeling qualified products by using a linear labeling machine;
(9) and (6) packaging.
Example 3
The formula of linezolid injection is the same as that in example 1, and the preparation method of the linezolid injection comprises the following steps:
(1) washing a rubber plug: cleaning the rubber plug by using a full-automatic rubber plug cleaning machine;
(2) weighing: weighing the linezolid, anhydrous citric acid, sodium hydroxide and sodium chloride according to the prescription amount respectively;
(3) preparation: adding water for injection into a concentration preparation tank to 90% of the total amount, controlling the temperature to be 60-65 ℃, putting weighed anhydrous citric acid and sodium hydroxide into the concentration preparation tank, stirring to completely dissolve the citric acid and the sodium hydroxide, adding weighed linezolid, stirring to completely dissolve the linezolid, adding weighed sodium chloride, stirring to completely dissolve the sodium chloride, keeping the temperature of the liquid medicine to be 60-65 ℃ in the preparation process, transferring the liquid medicine to a dilution preparation tank, supplementing the water for injection to the total amount, stirring until the liquid medicine is uniformly mixed, finishing the preparation, and detecting the pH value of the liquid medicine to be 4.8;
(4) and (3) filtering: a. primary filtration: the liquid medicine is primarily filtered by a first filter element (a polyether sulfone filter element, the aperture is 0.45 mu m, and the length is 10 inches); b. and (3) post-stage filtration: the liquid medicine is post-filtered by a second filter element (a polyether sulfone filter element, the aperture is 0.22 mu m, and the length is 10 inches);
(5) bottle washing and filling and sealing: washing and filling are carried out simultaneously, a washing machine is used for washing the borosilicate infusion bottle, and the washed infusion bottle is a thin layer without surface stains, flow marks and matt when being checked by eyes; filling the filtered liquid medicine into an infusion bottle by using a filling and nitrogen-filling corker, filling 300mL (the detection qualified standard is 300 plus 310mL) into each bottle, filling nitrogen into the bottle mouth, wherein the nitrogen pressure is 0.1MPa, and when the headspace oxygen content is detected to be less than 1%, adding a rubber plug and rolling an aluminum cap by using a capping machine;
(6) and (3) sterilization: sterilizing with a water bath sterilizer at 121 deg.C for 15 min;
(7) quality inspection: performing light inspection to remove unqualified products (glass, fiber, white blocks and other visible foreign matters, a small amount of the foreign matters, excessive amount of the foreign matters) and cracked bottles;
(8) labeling: labeling qualified products by using a linear labeling machine;
(9) and (6) packaging.
Example 4
The formula of linezolid injection is the same as that in example 1, and the preparation method of the linezolid injection comprises the following steps:
(1) washing a rubber plug: cleaning the rubber plug by using a full-automatic rubber plug cleaning machine;
(2) weighing: weighing the linezolid, anhydrous citric acid, sodium hydroxide and sodium chloride according to the prescription amount respectively;
(3) preparation: adding injection water into a concentration tank to 90% of the total amount, controlling the temperature to be 60-65 ℃, filling nitrogen under the liquid surface, wherein the nitrogen pressure is 0.6MPa, detecting that the dissolved oxygen amount in the injection water is less than 2ppm, putting weighed anhydrous citric acid and sodium hydroxide into the concentration tank, stirring to completely dissolve the anhydrous citric acid and the sodium hydroxide, adding weighed linezolid, stirring to completely dissolve the linezolid, adding weighed sodium chloride, stirring to completely dissolve the sodium chloride, keeping the temperature of the liquid medicine to be 60-65 ℃ in the preparation process, continuously filling nitrogen under the liquid surface in the preparation process, wherein the nitrogen pressure is 0.6MPa, transferring the liquid medicine to a dilution tank, supplementing the injection water to the total amount, stirring to be uniform, filling nitrogen under the liquid surface in the dilution tank in the process, wherein the nitrogen pressure is 0.6MPa, finishing the preparation, and detecting that the pH value of the liquid medicine is 4.8;
(4) and (3) filtering: a. primary filtration: the liquid medicine is primarily filtered by a first filter element (a polyether sulfone filter element, the aperture is 0.45 mu m, and the length is 10 inches); b. and (3) post-stage filtration: the liquid medicine is post-filtered by a second filter element (a polyether sulfone filter element, the aperture is 0.22 mu m, and the length is 10 inches);
(5) bottle washing and filling and sealing: washing and filling are carried out simultaneously, a washing machine is used for washing the borosilicate infusion bottle, and the washed infusion bottle is a thin layer without surface stains, flow marks and matt when being checked by eyes; filling the filtered liquid medicine into an infusion bottle by using a filling and nitrogen-filling corker, filling 300mL (the detection qualified standard is 300 plus 310mL) into each bottle, filling nitrogen into the bottle mouth, wherein the nitrogen pressure is 0.6MPa, and when the headspace oxygen content is detected to be less than 1%, adding a rubber plug and rolling an aluminum cap by using a capping machine;
(6) and (3) sterilization: sterilizing with a water bath sterilizer at 121 deg.C for 15 min;
(7) quality inspection: performing light inspection to remove unqualified products (glass, fiber, white blocks and other visible foreign matters, a small amount of the foreign matters, excessive amount of the foreign matters) and cracked bottles;
(8) labeling: labeling qualified products by using a linear labeling machine;
(9) and (6) packaging.
Comparative example
An injectable linezolid solution differs from example 1 only in that no nitrogen charge is performed during the formulation and encapsulation steps.
Examples of the experiments
The quality detection is respectively carried out on the self-made preparation of the linezolid injection prepared in the embodiments 1 to 4, the comparative preparation of the linezolid injection prepared in the comparative example and the reference preparation of the linezolid injection, and the detection indexes are as follows: the method comprises the following steps of detecting the content of the related substances, the impurity 3 and the linezolid by the following detection methods:
firstly, the detection method of related substances in linezolid injection comprises the following steps:
(1) mobile phase
Mobile phase A: precisely measuring 10mL of 10% trifluoroacetic acid solution, adding the 10mL of trifluoroacetic acid solution into 1000mL of water, and filtering by using a 0.45-micrometer membrane filter;
mobile phase B: precisely measuring 10mL of 10% trifluoroacetic acid solution, adding the 10mL of trifluoroacetic acid solution into 1000mL of acetonitrile, and filtering by using a 0.45-micrometer membrane filter;
diluting liquid: acetonitrile-water (10: 90).
(2) Test solution: taking the product as a test solution.
(3) Control solution: precisely measuring 1mL of the test solution, placing the test solution in a 100mL measuring flask, dissolving the test solution by using a diluent, diluting the test solution to a scale, and shaking up.
(4) Chromatographic conditions
A chromatographic column: YMC-Pack ODS-AM (150X 4.6mm, 5 μm)
Column temperature: at room temperature
Detection wavelength: 254nm
Flow rate: 1.0mL/min
Sample introduction amount: 10 μ L
And (3) an elution mode: gradient elution, elution procedure is shown in table 4.
TABLE 4 elution procedure
Note: td is the mixer inlet to column head delay time
(5) Sample detection
And respectively precisely measuring 10 mu L of the diluent, the test solution and the control solution, injecting and measuring, deducting a blank solvent peak, and calculating the amount of the related substances according to a self-control method.
Secondly, the method for detecting the impurity 3 in the linezolid injection comprises the following steps:
(1) test solution: taking 1mL of linezolid injection, placing the linezolid injection into a 10mL measuring flask, adding water to dilute the linezolid injection to a scale mark, and shaking up the linezolid injection.
(2) Control solution: and (3) precisely weighing a proper amount of impurity 3 reference substance, adding acetonitrile to dissolve and dilute the reference substance to prepare a solution containing the impurity 3 reference substance of 0.1ng/mL, 1ng/mL, 2ng/mL, 4ng/mL, 12ng/mL and 20ng/mL per 1mL, and obtaining the reference substance solution 1-6.
(3) Sample detection
Detecting the content of the impurity 3 by using a liquid chromatography-mass spectrometry method, respectively injecting sample solutions 1-6 of a test sample solution and a reference substance solution, and obtaining the content of the impurity 3 in the test sample solution by adopting an external standard method, wherein the liquid phase conditions and the mass spectrum conditions are shown in Table 5.
TABLE 5 liquid phase and Mass Spectrometry conditions for the detection of impurity 3 in linezolid injection
The standard curve is obtained as shown in fig. 1 (y-1,549.3186 x +566.6447, R)2.00000.9988), the MRM spectra of impurity 3 control, home-made preparations prepared in examples 1-4, comparative preparation, and reference preparation, detected as impurity 3, are shown in fig. 2-8.
The method for measuring the content of linezolid in the linezolid injection comprises the following steps:
(1) mobile phase
Mobile phase A: precisely measuring 10mL of 10% trifluoroacetic acid solution, adding the 10mL of trifluoroacetic acid solution into 1000mL of water, and filtering by using a 0.45-micrometer membrane filter;
mobile phase B: precisely measuring 10mL of 10% trifluoroacetic acid solution, adding the 10mL of trifluoroacetic acid solution into 1000mL of acetonitrile, and filtering by using a 0.45-micrometer membrane filter;
mobile phase: mobile phase a-mobile phase B (80: 20);
diluting liquid: acetonitrile-water (10: 90).
(2) Test solution: precisely measuring 5mL of the product, placing the product in a 100mL measuring flask, diluting the product to a scale with a diluent, and shaking up.
(3) Control solution: the linezolid control is about 10mg, precisely weighed, placed in a 100mL measuring flask, dissolved by adding 10mL acetonitrile, diluted to the scale by adding water, and shaken up.
(4) Chromatographic conditions
A chromatographic column: YMC-Pack ODS-AM (150X 4.6mm, 5 μm)
Column temperature: at room temperature
Detection wavelength: 254nm
Flow rate: 1.0mL/min
Sample introduction amount: 10 μ L
Operating time: for 10 min.
(5) Sample detection
Respectively and precisely measuring 10 μ L of reference solution and sample solution, and measuring by external standard method.
The quality test results of the linezolid injection self-made preparation, the comparative preparation and the reference preparation are shown in table 6.
TABLE 6 linezolid injection quality test results
As shown in Table 6, the self-made preparations prepared in examples 1-4 of the present application satisfy the requirements of each investigation item; regarding 3-fluoro-4- (4-morpholinyl) aniline (impurity 3), the content of the impurity 3 in a reference preparation is 16.8ppm, and the content of the impurity 3 in a comparison preparation is 26.2ppm, while the content of the impurity 3 in a self-made preparation prepared by implementing 1-4 in the application is 3.6-5.2 ppm, compared with the reference preparation and the comparison preparation (without nitrogen charging operation), the content of the impurity 3 in linezolid injection can be obviously reduced by performing nitrogen charging protection in the preparation and/or encapsulation steps, the product quality and the medication safety of the linezolid injection are improved, and the medication risk of the linezolid injection is also obviously reduced by reducing the content of genotoxic impurities.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications therefrom are within the scope of the invention.
Claims (4)
1. The preparation method of linezolid injection comprises the steps of weighing, preparing, filtering, encapsulating and sterilizing, and is characterized in that the preparation step comprises the following steps: filling nitrogen below the liquid level of the water for injection, preparing the liquid medicine when the dissolved oxygen in the water for injection is less than 2ppm, and continuously filling nitrogen below the liquid level in the preparation process, wherein the nitrogen pressure is 0.3-0.6 MPa;
in the step of potting, comprising: filling liquid medicine, filling nitrogen on the liquid surface, and sealing; in the step of filling and sealing, nitrogen is filled on the liquid surface until the oxygen content in the headspace is less than 1% under the nitrogen pressure of 0.1-0.6 MPa;
the linezolid injection comprises the following components in percentage by volume: 2mg/mL of linezolid, 1.92mg/mL of anhydrous citric acid, 0.76mg/mL of sodium hydroxide, 9mg/mL of sodium chloride and the balance of water for injection.
2. The method for preparing linezolid injection according to claim 1, wherein the step of formulating comprises:
adding water for injection to 90% of the total amount, adding the prescription amount of raw materials and adjuvants to dissolve completely, adding water for injection to the total amount, mixing well,
wherein the temperature of the water for injection and the liquid medicine is kept between 60 and 65 ℃ in the preparation process.
3. The method for preparing linezolid injection according to claim 1 or 2, wherein the linezolid is administered to the patient in a single dose,
in the step of filtering, comprising: sequentially carrying out primary filtration on the prepared liquid medicine through a first filter element and carrying out post-filtration through a second filter element, wherein the first filter element adopts a polyether sulfone filter element with the aperture of 0.45 mu m, and the second filter element adopts a polyether sulfone filter element with the aperture of 0.22 mu m;
in the sterilization step, the sterilization temperature is 121 ℃ and the sterilization time is 15 min.
4. Linezolid injection prepared by the preparation method according to any one of claims 1 to 3.
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| CN113209010B (en) * | 2021-04-15 | 2023-03-21 | 石家庄四药有限公司 | Linezolid glucose injection and preparation method thereof |
| CN113171340B (en) * | 2021-05-07 | 2022-12-06 | 四川科伦药业股份有限公司 | Alanyl glutamine injection and production process thereof |
| CN113244169A (en) * | 2021-05-20 | 2021-08-13 | 石家庄四药有限公司 | Linezolid sodium chloride injection and preparation method thereof |
| CN113588848B (en) * | 2021-07-21 | 2023-06-06 | 江苏吴中医药集团有限公司 | Pretreatment solution, pretreatment method and detection method of linezolid glucose solution |
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| CN102643251B (en) * | 2012-04-17 | 2016-08-10 | 四川美大康佳乐药业有限公司 | degradation impurity of linezolid and preparation method thereof |
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