CN113325108B - Sample pretreatment method of tacrolimus ointment - Google Patents

Sample pretreatment method of tacrolimus ointment Download PDF

Info

Publication number
CN113325108B
CN113325108B CN202110623436.6A CN202110623436A CN113325108B CN 113325108 B CN113325108 B CN 113325108B CN 202110623436 A CN202110623436 A CN 202110623436A CN 113325108 B CN113325108 B CN 113325108B
Authority
CN
China
Prior art keywords
extraction
tacrolimus
sample
carbon dioxide
tacrolimus ointment
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202110623436.6A
Other languages
Chinese (zh)
Other versions
CN113325108A (en
Inventor
朱召贞
曹慧敏
王守彬
吕敏
董双喜
刘宗银
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Jinan Zhongzhi Kangcheng Pharmaceutical Research And Development Co ltd
Original Assignee
Shandong Tingke Pharmaceutical Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shandong Tingke Pharmaceutical Co ltd filed Critical Shandong Tingke Pharmaceutical Co ltd
Priority to CN202110623436.6A priority Critical patent/CN113325108B/en
Publication of CN113325108A publication Critical patent/CN113325108A/en
Priority to PCT/CN2022/079963 priority patent/WO2022252730A1/en
Priority to ZA2022/02828A priority patent/ZA202202828B/en
Application granted granted Critical
Publication of CN113325108B publication Critical patent/CN113325108B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/06—Preparation
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/06—Preparation
    • G01N2030/062—Preparation extracting sample from raw material
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids

Landscapes

  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses a method for detecting tacrolimus ointment related substances, wherein supercritical fluid is adopted for extracting the tacrolimus related substances in the pretreatment of a sample, and the problems of incomplete extraction of the tacrolimus ointment related substances and over-complicated steps in the prior art are mainly solved.

Description

Sample pretreatment method of tacrolimus ointment
Technical Field
The invention belongs to the field of detection of medical products, and particularly relates to a method for detecting substances related to tacrolimus ointment.
Background
When the tacrolimus ointment related substances are detected, extraction of the tacrolimus related substances is the key of detection, and in the prior art, a sample pretreatment process adopts a solid-phase extraction method to obtain a test solution, and the method comprises the following specific steps of: pretreating the solid phase extraction column, adding n-hexane-ethyl acetate into a sample for suspension, centrifuging, and taking supernate to pass through the pretreated solid phase extraction column; adding n-hexane-ethyl acetate into the centrifugal tube for suspension, centrifuging, and taking supernate to pass through a pretreated solid phase extraction column; washing the solid phase extraction column with n-hexane-ethyl acetate for 6 times to ensure complete washing each time; and then eluting the solid phase extraction column twice by using ethyl acetate, collecting eluent, evaporating in a water bath to obtain oily residue, and adding a n-hexane-n-butyl chloride-acetonitrile mixed solution for dissolving to obtain a test sample solution. The treatment is complicated and inefficient, and operators can not extract related substances in the tacrolimus ointment completely due to insufficient experience, and sometimes, the extraction is effective for up to one day at a time, so that the current method is difficult to detect effectively.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a method for detecting tacrolimus ointment related substances, wherein supercritical fluid is adopted for extracting the tacrolimus related substances in the pretreatment of a sample, and the problems of incomplete extraction and over-complicated steps of the tacrolimus ointment related substances in the prior art are mainly solved.
The technical scheme of the invention is realized as follows:
a method for detecting substances related to tacrolimus ointment comprises the steps of pretreating a sample and detecting the substances related to tacrolimus, wherein supercritical fluid is adopted for extracting the substances related to tacrolimus in the pretreatment of the sample;
the supercritical fluid extraction conditions are as follows: the supercritical fluid is carbon dioxide, the extraction temperature is 60-65 ℃, the extraction pressure is 20-35 MPa, the extraction time is 45-60 min, and the flow rate of the carbon dioxide is 0.1-0.8L/min.
Preferably, the conditions of the supercritical fluid extraction are: the supercritical fluid is carbon dioxide, the extraction temperature is 60-65 ℃, the extraction pressure is 25-30 MPa, the extraction time is 60min, and the flow rate of the carbon dioxide is 0.6-0.8L/min.
Wherein the pretreatment of the sample comprises the following specific steps:
taking a tacrolimus ointment sample, dissolving the tacrolimus ointment sample in a water bath at 60-65 ℃ by using an n-hexane solvent, spraying the tacrolimus ointment sample into an extraction kettle at the pressure of 20-35 MPa, simultaneously introducing a carbon dioxide fluid for extraction, allowing components which are easily soluble in carbon dioxide and n-hexane to flow into a separation kettle from the top of the extraction kettle, allowing components which are not easily soluble in carbon dioxide and n-hexane to remain in the extraction kettle, and after continuous circulating extraction is finished, taking the components remaining in the extraction kettle to dissolve by using an n-hexane-n-butylchloride-acetonitrile solvent, namely: a test solution.
The content of tacrolimus in the tacrolimus ointment is 0.1 percent w/w, and the matrix is propylene carbonate, white vaseline, mineral oil, white wax and paraffin. During the pretreatment of the sample, the components which are not easy to dissolve in the carbon dioxide and the normal hexane comprise tacrolimus and propylene carbonate and remain in the extraction kettle, and the components which are easy to dissolve in the carbon dioxide and the normal hexane comprise white vaseline, mineral oil, white wax and paraffin wax and flow into the separation kettle from the top of the extraction kettle, so that the tacrolimus related substances are completely separated.
The volume ratio of the n-hexane-n-butyl chloride-acetonitrile is 1.
The detection of the tacrolimus related substances adopts a determination method of related substances published in the registration standard (standard number: JX 20130245) of imported drug tacrolimus ointment published by the State drug administration.
According to the detection method for the tacrolimus ointment related substances, the supercritical fluid is adopted for extracting the tacrolimus related substances in the pretreatment of the sample, the extraction is complete, the steps are simple, the tacrolimus related substances can be effectively extracted, the content of the tacrolimus ointment related substances is further accurately monitored, and the method plays an important role in the quality research of the tacrolimus ointment.
Drawings
FIG. 1 is an HPLC chromatogram of the tacrolimus drug substance;
FIG. 2 is HPLC chromatogram of blank adjuvant of the Tacrolimus ointment;
FIG. 3 is an HPLC chromatogram of the tacrolimus ointment related substance described in example 1;
FIG. 4 is an HPLC chromatogram of the tacrolimus ointment related substance described in example 2;
FIG. 5 is an HPLC chromatogram of the tacrolimus ointment related substance described in example 3;
FIG. 6 is an HPLC chromatogram of tacrolimus ointment related substances described in example 4;
FIG. 7 is a mass spectrum of a substance XV related to the high temperature damage of a tacrolimus bulk drug;
FIG. 8 is an HPLC chromatogram of tacrolimus ointment related substances when the test solution described in example 1 is left for 0 h;
FIG. 9 is an HPLC chromatogram of tacrolimus ointment related substances when the test solution described in example 1 is left for 1 h;
FIG. 10 is an HPLC chromatogram of tacrolimus ointment related substances when the test solution described in example 1 is left for 3 hours;
FIG. 11 is an HPLC chromatogram of tacrolimus ointment related substances when the test solution described in example 1 is left for 6 hours;
FIG. 12 is an HPLC chromatogram of tacrolimus ointment related substances when the test solution described in example 1 is left for 9 hours;
FIG. 13 is an HPLC chromatogram of tacrolimus ointment related substances when the test solution described in example 1 was left for 12 hours.
Detailed Description
The content of the tacrolimus in the tacrolimus ointment is 0.1 percent w/w, and the matrix is propylene carbonate, white vaseline, mineral oil, white wax and paraffin. Tacrolimus, propylene carbonate, white vaseline, mineral oil, white wax and paraffin used in the self-made tacrolimus ointment can be purchased and obtained from manufacturers published on the official website of CDE. The reference formulation used was tacrolimus ointment manufactured by anstelan pharmaceuticals (china) limited.
The formula of the tacrolimus ointment comprises the following components: tacrolimus 0.1% w/w, propylene carbonate 0.4g, white vaseline 10g, mineral oil 1.5g, white wax 1.5g, paraffin 1.5g.
Example 1
A method for detecting substances related to tacrolimus ointment comprises the following specific steps:
(1) Pretreatment of samples
Taking 10g of tacrolimus ointment sample, dissolving the tacrolimus ointment sample in a water bath at 60 ℃ by using an n-hexane solvent, spraying the tacrolimus ointment sample into an extraction kettle at the pressure of 25MPa, simultaneously introducing a carbon dioxide fluid with the flow rate of 0.7L/min for extraction for 60min, introducing a carbon dioxide fluid at the extraction temperature of 60 ℃, allowing components which are easily dissolved in carbon dioxide and n-hexane to flow into a separation kettle from the top of the extraction kettle, allowing components which are not easily dissolved in the carbon dioxide and the n-hexane to remain in the extraction kettle, and dissolving the components which remain in the extraction kettle by using 15mL of an n-hexane-n-butyl chloride-acetonitrile (volume ratio of 1: 1) solvent after continuous cyclic extraction is completed, namely: the test solution can be stored at room temperature for 12 hours.
(2) Detection of tacrolimus ointment related substances
The detection of the related substances adopts the determination method of the related substances published in the registration standard (standard number: JX 20130245) of imported drug tacrolimus ointment published by the State drug administration.
Precisely measuring 20 μ L of the sample solution and n-hexane-n-butylchloride-acetonitrile (volume ratio of 1: 1) solvent, respectively, injecting into a liquid chromatograph, and recording chromatogram until retention time of main component peak is 3 times. If an impurity peak exists in a chromatogram of a test solution, the impurity peak with the impurity content less than 0.1 percent can be ignored, and auxiliary material peaks before RRT =0.25 and about RRT =0.36 are deducted according to the calculation of an area normalization method. The isomer II and the isomer I are not counted into related substances, and among known impurities, the impurity XV (OD-1) cannot exceed 2.5 percent, and the rest of any single known impurity cannot exceed 1.0 percent; any single unknown impurity should not exceed 0.6%; the total impurities are not more than 5.0%.
Example 2
A method for detecting substances related to tacrolimus ointment comprises the following specific steps:
(1) Pretreatment of samples
Taking 10g of tacrolimus ointment sample, dissolving the tacrolimus ointment sample in a water bath at 65 ℃ by using an n-hexane solvent, spraying the tacrolimus ointment sample into an extraction kettle at the pressure of 30MPa, simultaneously introducing a carbon dioxide fluid with the flow rate of 0.6L/min for extraction for 45min, introducing a carbon dioxide fluid at the extraction temperature of 65 ℃, allowing components which are soluble in carbon dioxide and n-hexane to flow into a separation kettle from the top of the extraction kettle, allowing components which are not soluble in carbon dioxide and n-hexane to remain in the extraction kettle, and after continuous cyclic extraction is completed, taking the components remaining in the extraction kettle to be dissolved by using 15mL of the n-hexane-n-butylchloride-acetonitrile (volume ratio of 1: 1), namely: the test solution can be stored at room temperature for 12 hours.
(2) Detection of tacrolimus ointment related substances
The detection of the related substances adopts the determination method of the related substances published in the registration standard (standard number: JX 20130245) of imported drug tacrolimus ointment published by the State drug administration.
Precisely measuring 20 μ L of the sample solution and n-hexane-n-butylchloride-acetonitrile (volume ratio of 1: 1) solvent, respectively, injecting into a liquid chromatograph, and recording chromatogram until the retention time of main component peak is 3 times. If an impurity peak exists in a chromatogram of a test solution, the impurity peak with the impurity content of less than 0.1 percent can be ignored, and auxiliary material peaks before RRT =0.25 and around RRT =0.36 are deducted according to the calculation of an area normalization method. The isomer II and the isomer I are not counted into related substances, and among known impurities, the impurity XV (OD-1) cannot exceed 2.5 percent, and the rest of any single known impurity cannot exceed 1.0 percent; any single unknown impurity must not exceed 0.6%; the total impurities can not exceed 5.0 percent.
Example 3
A method for detecting substances related to tacrolimus ointment comprises the following specific steps:
(1) Pretreatment of samples
Taking 10g of tacrolimus ointment sample, dissolving the tacrolimus ointment sample in a water bath at 62 ℃ by using an n-hexane solvent, spraying the tacrolimus ointment sample into an extraction kettle at the pressure of 20MPa, simultaneously introducing a carbon dioxide fluid with the flow rate of 0.8L/min for extraction for 50min, introducing a carbon dioxide fluid at the extraction temperature of 62 ℃, allowing components which are easily dissolved in carbon dioxide and n-hexane to flow into a separation kettle from the top of the extraction kettle, allowing components which are not easily dissolved in carbon dioxide and n-hexane to remain in the extraction kettle, and dissolving the components remaining in the extraction kettle by using 15mL of the n-hexane-n-butylchloride-acetonitrile (volume ratio of 1: 1) solvent after continuous circulation extraction is completed, namely: the test solution can be stored at room temperature for 12 hours.
(2) Detection of tacrolimus ointment related substances
The detection of the related substances adopts the determination method of the related substances published in the registration standard (standard number: JX 20130245) of imported drug tacrolimus ointment published by the State drug administration.
Precisely measuring 20 μ L of the sample solution and n-hexane-n-butylchloride-acetonitrile (volume ratio of 1: 1) solvent, respectively, injecting into a liquid chromatograph, and recording chromatogram until the retention time of main component peak is 3 times. If an impurity peak exists in a chromatogram of a test solution, the impurity peak with the impurity content less than 0.1 percent can be ignored, and auxiliary material peaks before RRT =0.25 and about RRT =0.36 are deducted according to the calculation of an area normalization method. The isomer II and the isomer I are not counted into related substances, and among known impurities, the impurity XV (OD-1) cannot exceed 2.5 percent, and the rest of any single known impurity cannot exceed 1.0 percent; any single unknown impurity must not exceed 0.6%; the total impurities are not more than 5.0%.
Example 4
A method for detecting substances related to tacrolimus ointment comprises the following specific steps:
(1) Pretreatment of samples
Taking 10g of tacrolimus ointment sample, dissolving the tacrolimus ointment sample in a water bath at 60 ℃ by using an n-hexane solvent, spraying the tacrolimus ointment sample into an extraction kettle at the pressure of 20MPa, simultaneously introducing a carbon dioxide fluid with the flow rate of 0.8L/min for extraction for 60min, introducing a carbon dioxide fluid at the extraction temperature of 60 ℃, allowing components which are soluble in carbon dioxide and n-hexane to flow into a separation kettle from the top of the extraction kettle, allowing components which are not soluble in carbon dioxide and n-hexane to remain in the extraction kettle, and after continuous cyclic extraction is completed, taking the components remaining in the extraction kettle to be dissolved by using 15mL of the n-hexane-n-butylchloride-acetonitrile (volume ratio of 1: 1), namely: the test solution can be stored for 12 hours at room temperature.
(2) Detection of tacrolimus ointment related substances
The detection of the related substances adopts the determination method of the related substances published in the registration standard (standard number: JX 20130245) of imported drug tacrolimus ointment published by the State drug administration.
Precisely measuring 20 μ L of the sample solution and n-hexane-n-butylchloride-acetonitrile (volume ratio of 1: 1) solvent, respectively, injecting into a liquid chromatograph, and recording chromatogram until the retention time of main component peak is 3 times. If an impurity peak exists in a chromatogram of a test solution, the impurity peak with the impurity content less than 0.1 percent can be ignored, and auxiliary material peaks before RRT =0.25 and about RRT =0.36 are deducted according to the calculation of an area normalization method. The isomer II and the isomer I are not counted into related substances, and among known impurities, the impurity XV (OD-1) cannot exceed 2.5 percent, and the rest of any single known impurity cannot exceed 1.0 percent; any single unknown impurity should not exceed 0.6%; the total impurities are not more than 5.0%.
TABLE 1 Tacrolimus related substances relative retention time table
Related substances Relative retention time
Related substance VIII 0.61-0.65
Related substance IX 0.69-0.74
Related substance XV (OD-1) 0.75-0.79
Related substance XI 0.82-0.87
Unknown substance A 0.91-0.97
Tacrolimus 1.00
Isomer II 1.09-1.19
Isomer I 1.43-1.57
Related substance VI 1.87-1.95
TABLE 2 HPLC spectrogram peak results of tacrolimus-related substances of the present invention
Figure BDA0003101015680000061
Figure BDA0003101015680000071
With reference to the accompanying drawings 1-6, the blank auxiliary peak is deducted, and table 2 shows the relative retention time table of tacrolimus related substances (table 1) published in the registration standard of tacrolimus ointment (standard number: JX 20130245) as an imported drug published by the national drug administration: peak 1, peak 2, peak 3 and Peak 4 are related substance XV (OD-1), unknown substance, tacrolimus and isomer II, respectively.
From page 6 of the tacrolimus ointment 0.1% if file (japanese standard classification of commodities No. 872699 revised 7 months in 2018 (19 th edition)): the thermal decomposition of tacrolimus may produce related substance IX, related substance XI and related substance XV. The tacrolimus bulk drug adopted in the tacrolimus ointment is subjected to high-temperature damage to obtain a related mass spectrogram diagram 7, which shows a molecular ion peak [ M [ ] + NH 4 ]821.51580, consistent with the molecular weight of the related substance XV.
Stability testing of the test article solutions described in example 1:
after the sample solution prepared in the step (1) in the example 1 is placed at room temperature for 0h, 1h, 3h, 6h, 9h and 12h, samples are respectively injected according to the step (2), the stability of the sample solution is observed according to HPLC spectrograms in the steps 8-13, the observation result is shown in Table 3, the sum of the peak area and the main peak area is calculated, and the test result shows that the content measurement result of the tacrolimus ointment related substances is not changed greatly compared with 0 hour after the sample solution is placed at room temperature for 12 hours, which indicates that the stability of the sample solution is good within 12 hours.
Table 3 results of stability test of the test solutions described in example 1
Figure BDA0003101015680000081

Claims (3)

1. A sample pretreatment method of tacrolimus ointment is characterized in that: the pretreatment of the sample adopts supercritical fluid extraction; the conditions of the supercritical fluid extraction are as follows: the supercritical fluid is carbon dioxide, the extraction temperature is 60-65 ℃, the extraction pressure is 20-35 MPa, the extraction time is 45-60 min, and the flow rate of the carbon dioxide is 0.1-0.8L/min;
the pretreatment of the sample comprises the following specific steps:
taking a tacrolimus ointment sample, dissolving the tacrolimus ointment sample in a water bath at 60-65 ℃ by using an n-hexane solvent, spraying the tacrolimus ointment sample into an extraction kettle at the pressure of 20-35 MPa, simultaneously introducing a carbon dioxide fluid for extraction, allowing components which are easily soluble in carbon dioxide and n-hexane to flow into a separation kettle from the top of the extraction kettle, allowing components which are not easily soluble in carbon dioxide and n-hexane to remain in the extraction kettle, and after continuous circulating extraction is finished, taking the components remaining in the extraction kettle to dissolve by using an n-hexane-n-butylchloride-acetonitrile solvent, namely: a test solution;
the volume ratio of the n-hexane-n-butyl chloride-acetonitrile is 1.
2. The method for sample pretreatment of tacrolimus ointment according to claim 1, characterized in that: the supercritical fluid extraction conditions are as follows: the supercritical fluid is carbon dioxide, the extraction temperature is 60-65 ℃, the extraction pressure is 25-30 MPa, the extraction time is 60min, and the flow rate of the carbon dioxide is 0.6-0.8L/min.
3. The method for sample pretreatment of tacrolimus ointment according to claim 1, characterized in that: the content of tacrolimus in the tacrolimus ointment is 0.1 percent w/w, and the matrix is propylene carbonate, white vaseline, mineral oil, white wax and paraffin.
CN202110623436.6A 2021-06-04 2021-06-04 Sample pretreatment method of tacrolimus ointment Active CN113325108B (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
CN202110623436.6A CN113325108B (en) 2021-06-04 2021-06-04 Sample pretreatment method of tacrolimus ointment
PCT/CN2022/079963 WO2022252730A1 (en) 2021-06-04 2022-03-09 Method for detecting substances related to tacrolimus ointment
ZA2022/02828A ZA202202828B (en) 2021-06-04 2022-03-09 Detection method for tacrolimus ointment related substances

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202110623436.6A CN113325108B (en) 2021-06-04 2021-06-04 Sample pretreatment method of tacrolimus ointment

Publications (2)

Publication Number Publication Date
CN113325108A CN113325108A (en) 2021-08-31
CN113325108B true CN113325108B (en) 2022-12-09

Family

ID=77419688

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202110623436.6A Active CN113325108B (en) 2021-06-04 2021-06-04 Sample pretreatment method of tacrolimus ointment

Country Status (3)

Country Link
CN (1) CN113325108B (en)
WO (1) WO2022252730A1 (en)
ZA (1) ZA202202828B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113325108B (en) * 2021-06-04 2022-12-09 山东霆科药业有限公司 Sample pretreatment method of tacrolimus ointment
CN114428133B (en) * 2021-12-28 2023-06-09 江苏知原药业股份有限公司 Method for detecting content of impurity XV in tacrolimus ointment by using reversed phase chromatography

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5616595A (en) * 1995-06-07 1997-04-01 Abbott Laboratories Process for recovering water insoluble compounds from a fermentation broth
KR20060110915A (en) * 2005-04-20 2006-10-26 한미약품 주식회사 Method for preparing solid dispersion of sparingly water-soluble drug by using the supercritical antisolvent process
CN105769752A (en) * 2016-04-08 2016-07-20 湖北生物医药产业技术研究院有限公司 Method for preparing tacrolimus ointment and tacrolimus ointment
CN106946907A (en) * 2017-04-26 2017-07-14 华南理工大学 Method and the application of tacrolimus are isolated and purified from mycelium

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2297481T3 (en) * 2003-07-24 2008-05-01 Teva Gyogyszergyar Zartkoruen Mukodo Reszvenytarsasag METHOD FOR PURIFYING MACROLIDS.
US7575875B2 (en) * 2005-10-13 2009-08-18 Abbott Laboratories, Inc. Method of tacrolimus extraction and quantification using aqueous detergents
WO2013171490A1 (en) * 2012-05-17 2013-11-21 Micromass Uk Limited Method for determining the amount of an analyte by mass spectrometry with the|help of specially designed deuterated analyte analogs
CN103271826B (en) * 2013-05-15 2014-08-06 广东恒健制药有限公司 Industrial production method for Tacrolimus ointments
CN106226430A (en) * 2016-07-31 2016-12-14 合肥远志医药科技开发有限公司 A kind of relevant substance detecting method of tacrolimus formulations
CN109828038A (en) * 2017-11-23 2019-05-31 广州迈达康医药科技有限公司 A kind of application of solid-phase extraction column in tacrolimus formulations impurity analysis
CN113325108B (en) * 2021-06-04 2022-12-09 山东霆科药业有限公司 Sample pretreatment method of tacrolimus ointment

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5616595A (en) * 1995-06-07 1997-04-01 Abbott Laboratories Process for recovering water insoluble compounds from a fermentation broth
KR20060110915A (en) * 2005-04-20 2006-10-26 한미약품 주식회사 Method for preparing solid dispersion of sparingly water-soluble drug by using the supercritical antisolvent process
CN105769752A (en) * 2016-04-08 2016-07-20 湖北生物医药产业技术研究院有限公司 Method for preparing tacrolimus ointment and tacrolimus ointment
CN106946907A (en) * 2017-04-26 2017-07-14 华南理工大学 Method and the application of tacrolimus are isolated and purified from mycelium

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Analyses of marketplace tacrolimus drug product quality: Bioactivity, NMR and LC–MS;Cynthia D.Sommers 等;《Journal of Pharmaceutical and Biomedical Analysis》;20131130;第85卷;第108-117页 *
他克莫司软膏有关物质测定的影响因素分析;张兴哲 等;《中国药品标准》;20200930;第21卷(第5期);第435-439页 *
血药浓度分析的前处理方法及应用;张倩影 等;《广州化工》;20160630;第44卷(第11期);第10-12+41页 *

Also Published As

Publication number Publication date
WO2022252730A1 (en) 2022-12-08
ZA202202828B (en) 2022-06-29
CN113325108A (en) 2021-08-31

Similar Documents

Publication Publication Date Title
CN113325108B (en) Sample pretreatment method of tacrolimus ointment
AU2019395470B2 (en) Method for preparing cannabidiol by means of high-speed countercurrent chromatography separation and purification
AU2020102328A4 (en) Method for determination of heterocyclic aromatic amine in oil
WO2017173638A1 (en) Method for using squalene as identification marker of olive oil and camellia seed oil
JP6223364B2 (en) An improved analytical method for the analysis and determination of contaminants in dianhydrogalactitol
CN104198609A (en) Method for extracting compounds with pregnane mother nucleus structure from compositions
CN109212085A (en) The finger-print and its construction method of a kind of ganoderma lucidum spore oil and application
CN102070652B (en) Method for separating and extracting Sirolimus from fermentation liquid
CN114392287A (en) Pine needle extract for inhibiting activity of 5 alpha reductase as well as preparation method and application thereof
CN107589206B (en) Tobacco maleic hydrazide and glucoside quantitative analysis method thereof based on liquid chromatography-tandem mass spectrometry
CN103784480A (en) Preparation method and application of Armillaria luteo-virens antioxidant active component
Vetrova et al. Synthesis of phenanthrene alkaloids from herbal aporphine alkaloids in subcritical water using synthesis of seco-glaucine as an example
CN103235067A (en) Method for enriching gallotannin with antioxidation activity from mangos
CN114524793A (en) Method for extracting and purifying procyanidine from peanut skin
CN102590395A (en) Pretreatment method for lincomycin fermentation liquor for HPLC (High Performance Liquid Chromatography) analysis
CN105954420A (en) Rapid detection method for ligustrazine in balsamic salad dressing at eight degrees
CN112694486A (en) Solid-liquid separation method for tacrolimus fermentation liquor
Zhao et al. Determination of the origin of progesterone in butter by gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS)
CN118440091A (en) Separation method of aflatoxins B2 and G2 and chiral isomers thereof
CN109956984B (en) Method for extracting and separating nicotiflorin from China rose
CN103983711A (en) Kinsenoside quantitative analysis and detection method
CN113063869B (en) Qualitative analysis method of flavones extract of stem and leaf of prinsepia utilis royle
CN110716001B (en) Method for detecting characteristic spectrum of compound phellodendron amurense liquid preparation
CN109232674B (en) Method for extracting chrysin-8-C-beta-D-glucoside from Nanshan tea
CN102924557A (en) Triterpene compounds, preparation methods and applications thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
TA01 Transfer of patent application right

Effective date of registration: 20220224

Address after: 250000 floor 2, marketing center, baosida science and Technology Industrial Park, No. 8, Kaiyuan Road, Licheng District, Jinan City, Shandong Province

Applicant after: Shandong tingke Pharmaceutical Co.,Ltd.

Address before: 250100 Room 203, 2f, marketing center, baosida science and Technology Industrial Park, No. 8, Kaiyuan Road, Licheng District, Jinan City, Shandong Province

Applicant before: Shandong Guanxiu biopharmaceutical Co.,Ltd.

TA01 Transfer of patent application right
GR01 Patent grant
GR01 Patent grant
TR01 Transfer of patent right

Effective date of registration: 20230828

Address after: Room 304, 3rd Floor, Building 1, Mohai Industrial Park, No. 4 Taixing West Street, Jibei Street, Jiyang District, Jinan City, Shandong Province, 251400

Patentee after: Jinan Zhongzhi Kangcheng Pharmaceutical Research and Development Co.,Ltd.

Address before: 250000 floor 2, marketing center, baosida science and Technology Industrial Park, No. 8, Kaiyuan Road, Licheng District, Jinan City, Shandong Province

Patentee before: Shandong tingke Pharmaceutical Co.,Ltd.

TR01 Transfer of patent right