CN114295767A - Medicine impurity detection method based on propane fumarate tenofovir disoproxil tablets - Google Patents
Medicine impurity detection method based on propane fumarate tenofovir disoproxil tablets Download PDFInfo
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Abstract
The invention relates to a medicine impurity detection method based on a fumaric acid Propofol tenofovir disoproxil tablet, which comprises the following steps of S1, preparing a solution to be detected, wherein the solution to be detected comprises a sensitivity solution, a contrast solution, a system adaptability solution and a sample solution; step S2, starting a detection system to detect the content of each component in the solution to be detected, if the sensitivity of the current detection system does not meet the preset standard, adjusting the content and elution time of each mobile phase of each stage gradient in the detection system according to the previous detection result stored by an information storage module by a central control unit, starting a cleaning device arranged in the chromatographic column, and acquiring the cleaning frequency to clean the chromatographic column according to the previous detection result stored by the information storage module by the central control unit; and step S3, the central control unit obtains the amount of each impurity of the propylene fumarate tenofovir disoproxil tablet according to the chromatogram of the solution to be detected, wherein the central control unit compares each impurity with the preset amount of each impurity to judge the amount of the current propylene fumarate tenofovir disoproxil tablet medicine.
Description
Technical Field
The invention relates to the field of medicine impurities, in particular to a medicine impurity detection method based on a fumaric acid propyl phenol tenofovir disoproxil fumarate tablet.
Background
Hepatitis B patients are 20 hundred million people worldwide, about 33 million people die of cirrhosis and primary liver cancer caused by hepatitis B every year, and China is in the first three. The valproic acid propane Tenofovir (TAF) is an antiviral potent drug for treating chronic hepatitis B of adults and teenagers, belongs to nucleoside (acid) drugs with Tenofovir Disoproxil Fumarate (TDF) and Entecavir (ETV) and is used for three first-line drugs in the global hepatitis B treatment guidelines. The currently developed anti-hepatitis B new drug, namely, the fumarate of the Propofovir disoproxil fumarate (TAF), in Jilidide USA, has stronger targeting and good tolerance than the fumarate of Tenofovir Disoproxil Fumarate (TDF), the dose is only 1/10, the renal toxicity and the bone toxicity are lower, but the price is extremely high ($ 1700/30 tablets). Therefore, China needs to solve the technical problems of synthesis of TAF raw materials and preparation processes of tablets thereof, realize industrial production, get rid of import drug dependence and mainly solve the important problem of shortage of high-quality imitation drugs.
Chinese patent ZL202111090944.9 discloses a method for detecting impurities in a raw material for synthesizing tenofovir disoproxil fumarate and application thereof, which solves the technical problem that the total amount of impurities in a finished product of the tenofovir disoproxil fumarate cannot be accurately detected by a method for detecting impurities in part of the raw material for synthesizing the tenofovir disoproxil fumarate.
Disclosure of Invention
Therefore, the invention provides a medicine impurity detection method based on the Propofovir fumarate tablets, which can solve the technical problem that the medicine quality cannot be obtained according to the detection result of the sensitivity of a detection system on each impurity of the medicine.
In order to achieve the above object, the present invention provides a pharmaceutical impurity detection method based on a propane fumarate tenofovir disoproxil fumarate tablet, comprising:
step S1, preparing a solution to be detected, wherein the solution to be detected comprises a sensitivity solution, a contrast solution, a system adaptability solution and a sample solution;
step S2, starting a detection system to detect the content of each component in a solution to be detected, wherein a central control unit compares the main component peak signal-to-noise ratio with a preset signal-to-noise ratio according to a sensitivity solution chromatogram to judge the sensitivity of the current detection system, if the sensitivity of the current detection system does not meet a preset standard, the central control unit adjusts the content and the elution time of each mobile phase of each stage gradient in the detection system according to a last detection result stored in an information storage module, starting a cleaning device in a chromatographic column, and the central control unit acquires cleaning frequency according to the last detection result stored in the information storage module to clean the chromatographic column;
and step S3, the central control unit obtains the amount of each impurity of the propylene fumarate tenofovir disoproxil tablet according to the chromatogram of the solution to be detected, wherein the central control unit compares each impurity with the preset amount of each impurity to judge the quality of the current propylene fumarate tenofovir disoproxil tablet medicament.
Further, the central control unit compares the signal-to-noise ratio al of the main component peak height in the sensitivity solution chromatogram with a preset signal-to-noise ratio to judge the sensitivity of the current detection system, wherein,
when AL is less than or equal to AL1, the central control unit judges that the sensitivity of the current detection system does not meet the standard, and adjusts the content of each mobile phase and each elution time in the gradient elution;
when AL1 is more than AL and less than AL2, the central control unit judges that the sensitivity of the current detection system does not meet the standard, and the central control unit starts a cleaning device in the chromatographic column of the detection system to wash the chromatographic column;
when AL is larger than or equal to AL2, the central control unit judges that the sensitivity of the current detection system meets the standard;
the central control unit presets a signal-to-noise ratio AL, sets a first preset signal-to-noise ratio AL1 and a second preset signal-to-noise ratio AL 2.
Further, when the signal to noise ratio acquired by the central control unit is between a first preset signal to noise ratio and a second preset signal to noise ratio, the central control unit acquires the cleaning frequency of the cleaning device according to the real-time flow fluctuation rate d of each gradient elution stage of the solution to be detected of the last detection data acquired by the sensor so as to wash the chromatographic column,
when D is less than or equal to D1, the central control unit selects a first cleaning frequency v1 to wash the chromatographic column;
when D1 is more than D and less than D2, the central control unit selects a second cleaning frequency v2 to wash the chromatographic column;
when D is larger than or equal to D2, the central control unit selects a third cleaning frequency v3 to wash the chromatographic column;
the central control unit presets a fluctuation rate D, sets a first preset fluctuation rate D1 and a second preset fluctuation rate D2, presets a cleaning frequency v, and sets a first preset cleaning frequency v1, a second preset cleaning frequency v2 and a third preset cleaning frequency v 3.
Further, the central control unit obtains real-time flow of each gradient elution stage of the solution to be detected to obtain real-time flow fluctuation rate d, and sets d = ((d1-d0)2+(d2-d0)2+···+(dn-d0)2) And/n, wherein d1 is the real-time flow rate obtained by the sensor in the first gradient elution stage, d2 is the real-time flow rate obtained by the sensor in the second gradient elution stage,. cndot. dn is the real-time flow rate obtained by the sensor in the nth gradient elution stage, and d0 is the average value of the real-time flow rates obtained by the sensors from the first gradient elution stage to the nth gradient elution stage, wherein n is the total number of gradient elution stages.
Further, the central control unit stores the previous detection data according to the information storage module, obtains the correction factor variation degree b according to a difference value between each impurity correction factor and a preset standard value of each impurity correction factor, and sets b = | b1-b10|/b10+ | b2-b20|/b20+ · · + | -Bk0|/Bk0, where b1 is the central control unit obtains the first impurity correction factor, b2 is the central control unit obtains the second impurity correction factor · · Bk, b10 is the central control unit preset first impurity correction factor standard value, b20 is the central control unit preset second impurity correction factor · · Bk0 is the central control unit preset k-th impurity correction factor standard value, and k is set as the total impurity number standard value.
Further, the central control unit obtains the correction factor change degree B to compare with the preset change degree B, and adjusts the selected cleaning frequency vp, wherein,
when B is not more than B1, the central control unit does not adjust the selected cleaning frequency;
when B1 < B < B2, the central control unit reduces the selected cleaning frequency vp to vp1, and sets vp1= vp x (1- (B-B1) x (B2-B)/(B1 x B2));
when B is larger than or equal to B2, the central control unit increases the selected cleaning frequency vp to vp2, and sets vp2= vp x (1+ (B-B2)/B2);
the central control unit presets a change degree B, sets a first preset change degree B1 and a second preset change degree B2, and p =1,2 and 3.
Further, the cleaning device comprises a sliding mechanism, a rotating mechanism arranged on the sliding mechanism and a spraying mechanism connected with the rotating mechanism, the central control unit presets a cleaning frequency V, and the central control unit compares the acquired cleaning frequency vpq of the cleaning device with the preset cleaning frequency to adjust the sliding speed of the sliding mechanism and the rotating speed of the rotating mechanism of the cleaning device, wherein,
when vpq is less than or equal to V1, the central control unit reduces the rotation speed vz of the rotating mechanism to vz1 and reduces the sliding speed vh of the sliding mechanism to vh 1;
when V1 < vpq < V2, the central control unit increases the rotation speed vz of the rotating mechanism by vz 2;
when vpq is larger than or equal to V2, the central control unit increases the rotation speed vz of the rotating mechanism to vz3 and increases the sliding speed vh of the sliding mechanism to vh 2;
the central control unit presets a cleaning frequency V, sets a first preset cleaning frequency V1, and sets a second preset cleaning frequency V2, q =1, 2.
Further, the central control unit obtains the cleaning device cleaning frequency vpq being equal to or less than a first preset cleaning frequency V1, the central control unit reduces the rotation speed vz of the rotating mechanism by vz1, sets vz1= vz x (1- (V1-vpq)/V1), reduces the sliding speed vh of the sliding mechanism to vh1, sets vh1= vh x (1- (V1-vpq)/V1, the central control unit obtains the cleaning device cleaning frequency vpq between a first preset cleaning frequency V1 and a second preset cleaning frequency V2, the central control unit increases the rotation speed vz of the rotating mechanism by vz2, sets vz2= vz x (1+ (V2-vpq) x (vpq-V1)/(V1 × V2)), the central control unit obtains the cleaning device cleaning frequency vpq being greater than the second preset cleaning frequency 2, and increases the rotation speed vz3, vz3= vz × (1+ (vpq-V2)/V2), the sliding speed vh of the sliding mechanism is increased to vh2, and vh2= vh × (1+ (vpq-V2)/V2) is set.
Further, the signal-to-noise ratio of the main component peak height in the sensitivity solution chromatogram acquired by the central control unit is less than or equal to a first preset signal-to-noise ratio, the central control unit judges that the sensitivity of the current detection system does not meet the standard, the central control unit adjusts the content of the mobile phase in each stage in the gradient elution according to the last detection data, the obtained tailing factor Ti of each peak and the preset ith peak tailing factor Ti0, wherein,
when Ti is less than or equal to Ti0, the central control unit obtains the separation degree to adjust the elution time of each gradient stage;
when Ti is more than Ti0, the central control unit reduces the ratio of the first mobile phase and the second mobile phase in the i-th stage gradient elution to Gi1, and sets Gil = Gi x (1- (Ti-Ti0)/Ti0), wherein the content of the first mobile phase mi1 in the i-th stage gradient elution is adjusted to mi1, mi11= mi1/Gi × Gil, the content of the second mobile phase mi2 in the i-th stage gradient elution is adjusted to mi21, and mi21=100-mi 11.
Further, the central control unit acquires the last detection data, compares the adjacent peak separation degree ti of the liquid to be detected with a preset separation degree standard value, and adjusts the gradient elution time of the ith stage, wherein,
when ti is less than or equal to W0, the central control unit increases the elution time ei to ei1 in the i-stage gradient stage, and sets ei1= ei x (1+ (W0-ti)/W0);
when ti > W0, the central control unit shortened the i-th stage gradient elution time ei to ei2, setting ei2= ei x (1- (ti-W0)/W0).
Compared with the prior art, the invention has the advantages that the invention is provided with the central control unit which obtains the impurity amount of each drug of the propiofurazole fumarate tablet according to the content of each component, and comparing the amount of each impurity with the amount of each preset impurity, if the amount of each impurity of the current Propofovir disoproxil fumarate tablet is less than the amount of each preset impurity, meanwhile, the central control unit obtains that the total amount of the drug impurities of the current Propofol fumarate tenofovir tablet is less than the preset total amount of the impurities, the central control unit judges that the current Propofol fumarate tenofovir tablet is qualified, if the total amount of the drug impurities of the current Propofol fumarate tenofovir tablet is more than or equal to the preset total amount of the impurities, the central control unit obtains that the total amount of the drug impurities of the current Propofol fumarate tenofovir tablet is greater than or equal to the preset total amount of the impurities, and the central control unit judges that the current Propofol fumarate tenofovir tablet is unqualified; the central control unit compares the main component peak height signal-to-noise ratio with a preset signal-to-noise ratio according to the sensitivity solution chromatogram to judge the sensitivity of the current detection system, if the sensitivity of the current detection system does not meet the preset standard, the central control unit adjusts the content and the elution time of each mobile phase of each stage gradient arranged in the detection system according to the last detection result stored by the information storage module, starts a cleaning device arranged in the chromatographic column, and acquires the cleaning frequency according to the last detection result stored by the information storage module to clean the chromatographic column so as to enable the amount of impurities acquired by the chromatographic column to meet the standard;
in particular, the invention obtains the signal-to-noise ratio of the main component peak height of the chromatogram according to the sensitivity solution chromatogram, namely obtains the signal-to-noise ratio of the peak height of the Propofovir, the central control unit compares the obtained signal-to-noise ratio with the preset signal-to-noise ratio to judge whether the sensitivity of the current detection system meets the standard or not, wherein if the signal-to-noise ratio obtained by the central control unit is less than or equal to the first preset signal-to-noise ratio, the sensitivity of the current detection system is too poor, the central control unit adjusts the content of each mobile phase and each elution time in the preset gradient elution, if the signal-to-noise ratio obtained by the central control unit is between the first preset signal-to-noise ratio and the second preset signal-to-noise ratio, the sensitivity of the current detection system is poor, the central control unit cleans the chromatographic column through a detection device in the chromatographic column of the detection system to improve the sensitivity of the detection system until the central control unit judges that the sensitivity of the current detection system meets the standard, the signal-to-noise ratio acquired by the central control unit is greater than or equal to a second preset signal-to-noise ratio, the central control unit judges that the sensitivity of the current detection system meets the standard, and the detection is started for each component of the system applicability solution, the control solution and the sample solution.
In particular, when the control unit determines that the chromatographic column needs to be washed, the central control unit calls real-time flow of each gradient elution stage of the solution to be detected of the last detection data recorded in the information storage module to obtain the fluctuation rate of the real-time flow, and evaluates each gradient elution degree, wherein if the real-time flow fluctuation rate obtained by the central control unit is smaller than or equal to a first preset fluctuation rate, the real-time flow fluctuation rate obtained by the central control unit for the last detection data is smaller, namely the current chromatographic column has less impurities, the central control unit selects a smaller cleaning frequency to wash the chromatographic column, if the real-time fluctuation rate obtained by the central control unit is between the first preset fluctuation rate and a second preset fluctuation rate, the current chromatographic column has more impurities, the central control unit selects the second cleaning frequency to increase the washing frequency of the chromatographic column, and if the real-time fluctuation rate obtained by the central control unit is larger than or equal to the second preset fluctuation rate, and (3) indicating that the impurities of the current chromatographic column are excessive, and selecting a third preset cleaning frequency by the central control unit to wash the chromatographic column so as to enable the elution of the chromatographic column to the solution to be detected to meet the standard.
Particularly, the invention comprehensively evaluates whether the acquisition of the correction factor is accurate according to the ratio of the difference value of each impurity correction factor and the standard value of each preset impurity correction factor to the standard value, and acquires whether the correction factor is accurate or not for adjusting the definition frequency to better clean the dirt in the chromatographic column, wherein if the change degree of the correction factor acquired by the central control unit is less than or equal to a first preset change degree, the change degree of the current correction factor is in accordance with the standard, the central control unit does not adjust the selected cleaning frequency, if the change degree of the correction factor acquired by the central control unit is between the first preset change degree and a second preset change degree, the central control unit increases the cleaning frequency, so that the cleaning device can clean the chromatographic column in accordance with the dirt in the chromatographic column to solve the problem that the change degree of the correction factor is not in accordance with the standard, and if the change degree of the correction factor acquired by the central control unit is greater than or equal to the second preset change degree, the current correction factor is obtained extremely inaccurately, and the central control unit greatly improves the cleaning frequency so as to solve the problem of more dirt on the chromatographic column and avoid eluting impurities to adsorb and change the stationary phase.
In particular, the invention is provided with a cleaning device in the chromatographic column, comprehensively adjusts the rotating speed of a rotating mechanism and the sliding speed of a sliding mechanism in the cleaning device so as to match each adjusted parameter with the acquired cleaning frequency, the central control unit obtains the cleaning frequency which is less than or equal to a first preset cleaning frequency, simultaneously reduces the rotating frequency of the rotating mechanism and the sliding speed of the sliding mechanism to adjust the cleaning frequency of the cleaning device, obtains the cleaning frequency between the first preset cleaning frequency and a second preset cleaning frequency, improves the cleaning frequency by improving the rotating frequency of the rotating mechanism, obtains the cleaning frequency which is greater than or equal to the second preset cleaning frequency, and simultaneously improves the rotating frequency of the rotating mechanism and the sliding frequency of the sliding mechanism to comprehensively improve the cleaning frequency of the cleaning device.
Particularly, the method comprises the steps that according to the last detection data, the trailing factor of each peak obtained by the central control unit according to the chromatogram of the solution to be detected is used for evaluating whether the mobile phase and the elution time of each gradient elution process preset by the system are reasonable or not, wherein the trailing factor of each peak obtained by the central control unit is smaller than or equal to the preset trailing factor of the peak, the reason that the current sensitivity does not meet the standard is that the elution time of each gradient stage is unreasonable, the central control unit compares the separation degree of the adjacent peak of the liquid to be detected with the preset separation degree standard value to adjust the elution time of the gradient stage corresponding to the peak, if the obtained separation degree is smaller than or equal to the preset separation degree standard value, the central control unit improves the elution time of the gradient stage, and if the obtained separation degree is larger than the preset separation degree standard value, the central control unit reduces the elution time of the gradient stage; the central control unit obtains the tailing factor of each peak and is less than or equal to the preset tailing factor of the peak, the reason that the current sensitivity does not meet the standard is that the proportion of the first mobile phase and the second mobile phase in elution of each stage set by the system does not meet the standard, the central control unit reduces the proportion of the first mobile phase and the second mobile phase, namely, the content of the first mobile phase is reduced, the content of the second mobile phase is improved, the sensitivity of the detection system to liquid to be detected is improved, and the detection accuracy of the content of each impurity is improved.
Drawings
FIG. 1 is a schematic diagram of a drug impurity detection system based on a Propofovir fumarate tablet in an embodiment of the invention;
FIG. 2 is a schematic diagram of a chromatography column according to an embodiment of the invention;
fig. 3 is a schematic diagram of a drug impurity detection method based on a Propofovir fumarate tablet in an embodiment of the invention.
Detailed Description
In order that the objects and advantages of the invention will be more clearly understood, the invention is further described below with reference to examples; it should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Preferred embodiments of the present invention are described below with reference to the accompanying drawings. It should be understood by those skilled in the art that these embodiments are only for explaining the technical principle of the present invention, and do not limit the scope of the present invention.
It should be noted that in the description of the present invention, the terms of direction or positional relationship indicated by the terms "upper", "lower", "left", "right", "inner", "outer", etc. are based on the directions or positional relationships shown in the drawings, which are only for convenience of description, and do not indicate or imply that the device or element must have a specific orientation, be constructed in a specific orientation, and be operated, and thus, should not be construed as limiting the present invention.
Furthermore, it should be noted that, in the description of the present invention, unless otherwise explicitly specified or limited, the terms "mounted," "connected," and "connected" are to be construed broadly, and may be, for example, fixedly connected, detachably connected, or integrally connected; can be mechanically or electrically connected; they may be connected directly or indirectly through intervening media, or they may be interconnected between two elements. The specific meanings of the above terms in the present invention can be understood by those skilled in the art according to specific situations.
Fig. 1 is a schematic diagram of a drug impurity detection system based on a tenofovir disoproxil fumarate tablet according to an embodiment of the present invention, including a constant flow pump 1 for injecting a mobile phase into a chromatography column; the chromatographic column 2 is connected with the constant flow pump and is used for separating each component of the solution; the detector 3 is connected with the chromatographic column and is used for acquiring data information according to a chromatogram of the solution to be detected, wherein the data information comprises the content of each component of the solution to be detected, a peak area, a peak height, a tailing factor and the separation degree of adjacent peaks; a central control unit 4, which comprises an information storage module for storing the chromatogram map and the data information of each detection frequency, the central control unit obtains the impurity amount of each drug of the propylene fumarate tenofovir disoproxil tablet according to the content of each component, and comparing the amount of each impurity with the amount of each preset impurity, if the amount of each impurity of the current Propofovir disoproxil fumarate tablet is less than the amount of each preset impurity, meanwhile, the central control unit obtains that the total amount of the drug impurities of the current Propofol fumarate tenofovir tablet is less than the preset total amount of the impurities, the central control unit judges that the current Propofol fumarate tenofovir tablet is qualified, if the total amount of the drug impurities of the current Propofol fumarate tenofovir tablet is more than or equal to the preset total amount of the impurities, the central control unit obtains that the total amount of the drug impurities of the current Propofol fumarate tenofovir tablet is greater than or equal to the preset total amount of the impurities, and the central control unit judges that the current Propofol fumarate tenofovir tablet is unqualified;
the central control unit compares the main component peak height signal-to-noise ratio with a preset signal-to-noise ratio according to the sensitivity solution chromatogram to judge the sensitivity of the current detection system, if the sensitivity of the current detection system does not meet the preset standard, the central control unit adjusts the content and the elution time of each mobile phase of each stage gradient arranged in the detection system according to the last detection result stored by the information storage module, starts a cleaning device arranged in the chromatographic column, and acquires the cleaning frequency according to the last detection result stored by the information storage module to clean the chromatographic column so as to enable the amount of impurities acquired by the chromatographic column to meet the standard;
specifically, the total impurity amount of the propofol fumarate tenofovir tablets in the embodiments of the present invention is obtained by a method that an impurity peak exists in a chromatogram (excluding a solvent peak and a fumaric acid peak) of a sample solution, and the impurity content is calculated according to a self-comparison method of multiplying a correction factor, wherein each impurity amount is required to meet the corresponding limit specification in table three.
Please refer to fig. 2, which is a schematic diagram of a chromatography column structure according to an embodiment of the present invention, including that a cleaning device is disposed in the chromatography column 2, the cleaning device includes a sliding mechanism, a rotating mechanism disposed on the sliding mechanism, and a spraying mechanism 24 connected to the rotating mechanism, the spraying mechanism is connected to a liquid pipe 23 for injecting a cleaning liquid into the spraying mechanism, wherein the sliding mechanism includes a sliding rod 25 and a first motor 21 for controlling a rotation rate of the sliding rod, and the rotating mechanism includes a bearing 22 disposed on the sliding rod and a second motor for controlling a rotation speed of the bearing; when the adsorbed sample components accumulate to a certain extent in the column, a new stationary phase begins to form. The new detection substance can act with residual impurities to form a certain separation mechanism, so that retention time fluctuation is caused, and a tailing phenomenon is caused. Over time, the back pressure of the chromatographic column exceeds the maximum pressure that the pump can bear, so that the chromatographic column cannot work and a void volume is generated at the blockage position, and the detection result is influenced. The cleaning liquid in the cleaning device is not limited in the examples of the present invention as long as it can clean impurities in the chromatography column, and the examples of the present invention provide a preferable embodiment, i.e., one or more of 100% methanol, 100% acetonitrile, 75% acetonitrile-25% isopropanol, 100% dichloromethane, and 100% n-hexane. For example, a 250mm × 4.6mm chromatographic column can be washed with a flow rate of 1-2 ml/min, so that the washing frequency can be set to 1min per washing with 100% methanol, and the flow rate is 1ml, at this time, the sliding speed of the sliding mechanism is 250mm/min, and the rotating speed of the rotating mechanism is 25 r/min.
Please refer to fig. 3, which is a schematic diagram of a method for detecting impurities in a medicament based on a tenofovir disoproxil fumarate tablet according to an embodiment of the present invention, including,
step S1, preparing a solution to be detected, wherein the solution to be detected comprises a sensitivity solution, a contrast solution, a system adaptability solution and a sample solution;
step S2, starting a detection system to detect the content of each component in a solution to be detected, wherein a central control unit compares the main component peak signal-to-noise ratio with a preset signal-to-noise ratio according to a sensitivity solution chromatogram to judge the sensitivity of the current detection system, if the sensitivity of the current detection system does not meet a preset standard, the central control unit adjusts the content and the elution time of each mobile phase of each stage gradient in the detection system according to a last detection result stored in an information storage module, starting a cleaning device in a chromatographic column, and the central control unit acquires cleaning frequency according to the last detection result stored in the information storage module to clean the chromatographic column;
and step S3, the central control unit acquires the total amount of impurities according to the chromatogram of the solution to be detected, wherein the central control unit compares the total amount of impurities with the preset total amount of impurities to judge the quality of the current Propofovir fumarate tablet.
Specifically, in step S10 of the embodiment of the present invention, a solution to be tested is prepared, wherein step S10 includes steps S11 to S14,
step S11, taking a proper amount of fine powder (about 10mg equivalent to the Propofovir), precisely weighing, placing in a 20ml measuring flask, adding a first mobile phase for dissolving (shaking and ultrasonic, ultrasonic time is 7-8 minutes), diluting to a scale, shaking uniformly, filtering, and taking a subsequent filtrate as a sample solution;
step S12, precisely measuring a proper amount, adding a first mobile phase for quantitative dilution to prepare a solution containing about 5 mu g of the propofol tenofovir in each 1ml as a control solution;
step S13, precisely measuring a proper amount of the test solution, and adding a first mobile phase for quantitative dilution to prepare a solution containing about 0.25 mu g of the Propofovir per 1ml as a sensitivity solution;
and step S14, taking the product and a proper amount of each impurity reference substance, adding the first mobile phase for dissolving and diluting to prepare a mixed reference substance solution containing about 0.5mg of the Propofovir and 5 mu g of each impurity reference substance in each 1ml, and using the mixed reference substance solution as a system applicability solution.
Step S20, using octadecylsilane chemically bonded silica as filler, starting liquid chromatograph to respectively perform chromatographic analysis on 15 μ l of system applicability solution, 15 μ l of sensitivity solution, 15 μ l of control solution and 15 μ l of test solution;
and step S30, obtaining the total amount of impurities according to the chromatographic analysis result.
The central control unit compares the signal-to-noise ratio al of the main component peak height in the sensitivity solution chromatogram with a preset signal-to-noise ratio to judge the sensitivity of the current detection system, wherein,
when AL is less than or equal to AL1, the central control unit judges that the sensitivity of the current detection system does not meet the standard, and adjusts the content of each mobile phase and each elution time in the gradient elution;
when AL1 is more than AL and less than AL2, the central control unit judges that the sensitivity of the current detection system does not meet the standard, and the central control unit starts a cleaning device in the chromatographic column of the detection system to wash the chromatographic column;
when AL is larger than or equal to AL2, the central control unit judges that the sensitivity of the current detection system meets the standard;
the central control unit presets a signal-to-noise ratio AL, sets a first preset signal-to-noise ratio AL1 and a second preset signal-to-noise ratio AL 2.
Specifically, the invention obtains the signal-to-noise ratio of the main component peak height of the chromatogram according to the sensitivity solution chromatogram, namely obtains the signal-to-noise ratio of the peak height of the Propofovir, the central control unit compares the obtained signal-to-noise ratio with the preset signal-to-noise ratio to judge whether the sensitivity of the current detection system meets the standard or not, wherein if the signal-to-noise ratio obtained by the central control unit is less than or equal to the first preset signal-to-noise ratio, the sensitivity of the current detection system is too poor, the central control unit adjusts the content of each mobile phase and each elution time in the preset gradient elution, if the signal-to-noise ratio obtained by the central control unit is between the first preset signal-to-noise ratio and the second preset signal-to-noise ratio, the sensitivity of the current detection system is poor, the central control unit cleans the chromatographic column through a detection device in the chromatographic column of the detection system to improve the sensitivity of the detection system until the central control unit judges that the sensitivity of the current detection system meets the standard, the signal-to-noise ratio acquired by the central control unit is greater than or equal to a second preset signal-to-noise ratio, the central control unit judges that the sensitivity of the current detection system meets the standard, and the detection is started for each component of the system applicability solution, the control solution and the sample solution.
Specifically, when the signal to noise ratio acquired by the central control unit is between a first preset signal to noise ratio and a second preset signal to noise ratio, the central control unit acquires the cleaning frequency of the cleaning device according to the real-time flow fluctuation rate d of each gradient elution stage of the solution to be detected of the last detection data acquired by the sensor to flush the chromatographic column,
when D is less than or equal to D1, the central control unit selects a first cleaning frequency v1 to wash the chromatographic column;
when D1 is more than D and less than D2, the central control unit selects a second cleaning frequency v2 to wash the chromatographic column;
when D is larger than or equal to D2, the central control unit selects a third cleaning frequency v3 to wash the chromatographic column;
the central control unit presets a fluctuation rate D, sets a first preset fluctuation rate D1 and a second preset fluctuation rate D2, presets a cleaning frequency v, and sets a first preset cleaning frequency v1, a second preset cleaning frequency v2 and a third preset cleaning frequency v 3.
Specifically, the central control unit obtains real-time flow rate of each gradient elution stage of the solution to be detected to obtain real-time flow fluctuation rate d, and sets d = ((d1-d0)2+(d2-d0)2+···+(dn-d0)2) And/n, wherein d1 is the real-time flow rate obtained by the sensor in the first gradient elution stage, d2 is the real-time flow rate obtained by the sensor in the second gradient elution stage,. cndot. dn is the real-time flow rate obtained by the sensor in the nth gradient elution stage, and d0 is the average value of the real-time flow rates obtained by the sensors from the first gradient elution stage to the nth gradient elution stage, wherein n is the number of the gradient elution stages.
Specifically, when the control unit judges that the chromatographic column needs to be washed, the central control unit calls real-time flow of a solution to be detected of previous detection data recorded in the information storage module to obtain the fluctuation rate of the real-time flow at each gradient elution stage so as to evaluate the gradient elution degree, wherein if the real-time flow fluctuation rate obtained by the central control unit is smaller than or equal to a first preset fluctuation rate, the real-time flow fluctuation rate obtained by the central control unit for the previous detection data is smaller, namely the current chromatographic column has less impurities, the central control unit selects a smaller cleaning frequency to wash the chromatographic column, if the real-time fluctuation rate obtained by the central control unit is between the first preset fluctuation rate and a second preset fluctuation rate, the current chromatographic column has more impurities, the central control unit selects the second cleaning frequency to increase the washing frequency of the chromatographic column, and if the real-time fluctuation rate obtained by the central control unit is larger than or equal to the second preset fluctuation rate, and (3) indicating that the impurities of the current chromatographic column are excessive, and selecting a third preset cleaning frequency by the central control unit to wash the chromatographic column so as to enable the elution of the chromatographic column to the solution to be detected to meet the standard.
Specifically, the central control unit stores the last detection data according to the information storage module, obtains the correction factor variation degree b according to the difference between each impurity correction factor and a preset standard value of each impurity correction factor, and sets b = | b1-b10|/b10+ | b2-b20|/b20+ · | + | Bk-Bk0|/Bk0, where b1 is the central control unit obtaining the first impurity correction factor, b2 is the central control unit obtaining the second impurity correction factor · · Bk, b10 is the central control unit presetting first impurity correction factor standard value, b20 is the central control unit presetting second impurity correction factor standard value · · Bk0 is the central control unit presetting the kth impurity correction factor standard value, and k is the total number of impurities.
Wherein the central control unit obtains the correction factor change degree B to compare with the preset change degree B, and adjusts the selected cleaning frequency vp, wherein,
when B is not more than B1, the central control unit does not adjust the selected cleaning frequency;
when B1 < B < B2, the central control unit reduces the selected cleaning frequency vp to vp1, and sets vp1= vp x (1- (B-B1) x (B2-B)/(B1 x B2));
when B is larger than or equal to B2, the central control unit increases the selected cleaning frequency vp to vp2, and sets vp2= vp x (1+ (B-B2)/B2);
the central control unit presets a change degree B, sets a first preset change degree B1 and a second preset change degree B2, and p =1,2 and 3.
Specifically, the invention comprehensively evaluates whether the acquisition of the correction factor is accurate according to the ratio of the difference value of each impurity correction factor and the standard value of each preset impurity correction factor to the standard value, and acquires whether the correction factor is accurate or not for adjusting the definition frequency to better clean the dirt in the chromatographic column, wherein if the change degree of the correction factor acquired by the central control unit is less than or equal to a first preset change degree, the change degree of the current correction factor is in accordance with the standard, the central control unit does not adjust the selected cleaning frequency, if the change degree of the correction factor acquired by the central control unit is between the first preset change degree and a second preset change degree, the central control unit increases the cleaning frequency, so that the cleaning device can clean the chromatographic column in accordance with the dirt in the chromatographic column to solve the problem that the change degree of the correction factor is not in accordance with the standard, and if the change degree of the correction factor acquired by the central control unit is greater than or equal to the second preset change degree, the current correction factor is obtained extremely inaccurately, and the central control unit greatly improves the cleaning frequency so as to solve the problem of more dirt on the chromatographic column and avoid eluting impurities to adsorb and change the stationary phase.
Specifically, the cleaning device comprises a sliding mechanism, a rotating mechanism arranged on the sliding mechanism and a spraying mechanism connected with the rotating mechanism, the central control unit presets a cleaning frequency V, and adjusts the sliding speed of the sliding mechanism and the rotating speed of the rotating mechanism of the cleaning device according to the comparison between the acquired cleaning frequency vpq of the cleaning device and the preset cleaning frequency, wherein,
when vpq is less than or equal to V1, the central control unit reduces the rotation speed vz of the rotating mechanism to vz1 and reduces the sliding speed vh of the sliding mechanism to vh 1;
when V1 < vpq < V2, the central control unit increases the rotation speed vz of the rotating mechanism by vz 2;
when vpq is larger than or equal to V2, the central control unit increases the rotation speed vz of the rotating mechanism to vz3 and increases the sliding speed vh of the sliding mechanism to vh 2;
the central control unit presets a cleaning frequency V, sets a first preset cleaning frequency V1, and sets a second preset cleaning frequency V2, q =1, 2.
Specifically, the central control unit obtains the cleaning device cleaning frequency vpq being equal to or less than a first preset cleaning frequency V1, the central control unit reduces the rotation speed vz of the rotating mechanism by vz1, sets vz1= vz x (1- (V1-vpq)/V1), reduces the sliding speed vh of the sliding mechanism to vh1, sets vh1= vh x (1- (V1-vpq)/V1, the central control unit obtains the cleaning device cleaning frequency vpq between a first preset cleaning frequency V1 and a second preset cleaning frequency V2, the central control unit increases the rotation speed vz of the rotating mechanism by vz2, sets vz2= vz x (1+ (V2-vpq) x (vpq-V1)/(V1 × V2)), the central control unit obtains the cleaning device cleaning frequency vpq being equal to or greater than the second preset cleaning frequency V2, increases the rotation speed vz3, vz3= vz × (1+ (vpq-V2)/V2), the sliding speed vh of the sliding mechanism is increased to vh2, and vh2= vh × (1+ (vpq-V2)/V2) is set.
In particular, the invention is provided with a cleaning device in a chromatographic column, comprehensively adjusts the rotating speed of a rotating mechanism and the sliding speed of a sliding mechanism in the cleaning device so as to match each adjusted parameter with the acquired cleaning frequency, the central control unit obtains the cleaning frequency which is less than or equal to a first preset cleaning frequency, simultaneously reduces the rotating frequency of the rotating mechanism and the sliding speed of the sliding mechanism to adjust the cleaning frequency of the cleaning device, obtains the cleaning frequency between the first preset cleaning frequency and a second preset cleaning frequency, improves the cleaning frequency by improving the rotating frequency of the rotating mechanism, obtains the cleaning frequency which is greater than or equal to the second preset cleaning frequency, and simultaneously improves the rotating frequency of the rotating mechanism and the sliding frequency of the sliding mechanism to comprehensively improve the cleaning frequency of the cleaning device.
The central control unit obtains the signal to noise ratio of the height of the main component peak in the sensitivity solution chromatogram and is less than or equal to a first preset signal to noise ratio, the central control unit judges that the sensitivity of the current detection system does not meet the standard, the central control unit adjusts the content of the mobile phase at each stage in the gradient elution according to the last detection data and the obtained tailing factor Ti of each peak and the preset ith peak tailing factor Ti0, wherein,
when Ti is less than or equal to Ti0, the central control unit obtains the separation degree to adjust the elution time of each gradient stage;
when Ti is more than Ti0, the central control unit reduces the ratio of the first mobile phase to the second mobile phase in the i-stage gradient elution to Gi1, and sets Gil = Gi x (1- (Ti-Ti0)/Ti0), wherein the content of the first mobile phase mi1 in the i-stage gradient elution is adjusted to mi1, mi11= mi1/Gi × Gil, the content of the second mobile phase mi2 in the i-stage gradient elution is adjusted to mi21, and mi21=100-mi11;
wherein i =1,2 · n.
Specifically, the tailing factor obtaining object is not limited in the embodiment of the present invention, and the tailing factor can be calculated according to a chromatogram of a system adaptive solution and a sample solution, and an embodiment of the present invention provides a preferred embodiment, wherein the central control unit obtains, according to the chromatogram of the sample solution, a tailing factor corresponding to fumaric acid 1.2, a tailing factor corresponding to impurity 1.9, a tailing factor corresponding to impurity 2 1.3, a tailing factor corresponding to impurity 3 0.8, a tailing factor corresponding to impurity 4 1.2, a tailing factor corresponding to impurity 5 1.2, a tailing factor corresponding to impurity 6, a tailing factor corresponding to impurity 7 0.9, a tailing factor corresponding to impurity 8 1.0, a tailing factor corresponding to propofol tenofovir 1.4, a tailing factor corresponding to impurity 9, a tailing factor corresponding to impurity 10, and more specifically, one impurity is eluted in each step of gradient, corresponding to a peak diagram on a chromatogram, wherein the embodiment of the invention generates peaks according to the sequence of fumaric acid, impurity 1, impurity 2, impurity 3, impurity 4, impurity 5, impurity 6, impurity 7, impurity 8, propofol tenofovir, impurity 9 and impurity 10, the number of theoretical plates of a main peak in a system applicability solution is not less than 25000, a tailing factor is 0.8-1.5, and the separation degree of the main peak and adjacent peaks and the separation degree of each impurity peak meet requirements.
Wherein, the central control unit acquires the last detection data, compares the adjacent peak separation degree ti of the liquid to be detected with a preset separation degree standard value, and adjusts the gradient elution time of the i stage, wherein,
when ti is less than or equal to W0, the central control unit increases the elution time ei to ei1 in the i-stage gradient stage, and sets ei1= ei x (1+ (W0-ti)/W0);
when ti > W0, the central control unit shortened the i-th stage gradient elution time ei to ei2, setting ei2= ei x (1- (ti-W0)/W0).
Specifically, the embodiment of the present invention is not limited to the object of obtaining the separation degree of adjacent peaks, and the separation degree of adjacent peaks can be obtained according to the chromatograms of the system adaptive solution and the sample solution, and t1 represents the separation degree of a first peak from a second peak, t2 represents the separation degree of a second peak from a third peak, and up to t (n-1), the separation degree of an (n-1) th peak from an nth peak.
Specifically, the method comprises the steps that according to last detection data, a trailing factor of each peak is obtained according to a chromatogram of a solution to be detected so as to evaluate whether a mobile phase and elution time of each gradient elution process preset by a system are reasonable or not, wherein the trailing factor of each peak obtained by a central control unit is smaller than or equal to a preset trailing factor of the peak, which indicates that the reason that the current sensitivity does not meet a standard is that the elution time of each gradient stage is unreasonable, the central control unit compares the separation degree of adjacent peaks of the liquid to be detected with a preset separation degree standard value so as to adjust the elution time of the gradient stage corresponding to the peak, if the obtained separation degree is smaller than or equal to the preset separation degree standard value, the central control unit improves the elution time of the gradient stage, and if the obtained separation degree is larger than the preset separation degree standard value, the central control unit reduces the elution time of the gradient stage; the central control unit obtains the tailing factor of each peak and is less than or equal to the preset tailing factor of the peak, the reason that the current sensitivity does not meet the standard is that the proportion of the first mobile phase and the second mobile phase in elution of each stage set by the system does not meet the standard, the central control unit reduces the proportion of the first mobile phase and the second mobile phase, namely, the content of the first mobile phase is reduced, the content of the second mobile phase is improved, the sensitivity of the detection system to liquid to be detected is improved, and the detection accuracy of the content of each impurity is improved.
Specifically, the gradient elution time of each stage, the content of the first mobile phase and the second mobile phase are not limited as long as the gradient elution time can elute each impurity in the propofol fumarate tenofovir tablets, and the present embodiment provides a preferred embodiment, as shown in table one, wherein the first stage elutes fumaric acid, i.e., the first peak, the second stage elutes the first impurity, i.e., the second peak, the third stage elutes the second impurity, i.e., the third peak, the fourth stage elutes the third impurity, i.e., the fourth peak, the fifth stage elutes the fourth impurity, i.e., the fifth peak, the sixth stage elutes the fifth impurity, i.e., the sixth peak, the seventh stage elutes the sixth impurity, i.e., the eighth peak, the ninth stage elutes the eighth impurity, i.e., the ninth peak, the tenth stage elutes the propofol tenofovir, i.e., the tenth peak, and the eleventh stage elutes the ninth impurity, i.e., the eleventh peak, the twelfth stage elutes the tenth impurity, the twelfth peak. Wherein, the impurities of the Propofol fumarate tenofovir tablets are shown in the table II.
TABLE-gradient elution TABLE
Wherein the first mobile phase is 0.02mol/L phosphate buffer solution (pH6.0) - [ tetrahydrofuran-acetonitrile (7: 3) ] (99: 1), the second mobile phase is 0.02mol/L phosphate buffer solution (pH6.0) - [ tetrahydrofuran-acetonitrile (7: 3) ] (50: 50), the column temperature is 25 ℃ during detection, and the detection wavelength is 260 nm.
Basic information of each impurity of epidifumarate Propofovir tablets
Correction factors and limits for impurities in table III
Note: chromatographic peaks smaller than 2 times (0.10%) of the main peak area of the sensitivity solution in the chromatogram of the test solution are ignored.
So far, the technical solutions of the present invention have been described in connection with the preferred embodiments shown in the drawings, but it is easily understood by those skilled in the art that the scope of the present invention is obviously not limited to these specific embodiments. Equivalent changes or substitutions of related technical features can be made by those skilled in the art without departing from the principle of the invention, and the technical scheme after the changes or substitutions can fall into the protection scope of the invention.
Claims (10)
1. A drug impurity detection method based on a propane fumarate tenofovir disoproxil tablet is characterized by comprising the following steps:
step S1, preparing a solution to be detected, wherein the solution to be detected comprises a sensitivity solution, a contrast solution, a system adaptability solution and a sample solution;
step S2, starting a detection system to detect the content of each component in a solution to be detected, wherein a central control unit compares the main component peak signal-to-noise ratio with a preset signal-to-noise ratio according to a sensitivity solution chromatogram to judge the sensitivity of the current detection system, if the sensitivity of the current detection system does not meet a preset standard, the central control unit adjusts the content and the elution time of each mobile phase of each stage gradient in the detection system according to a last detection result stored in an information storage module, starting a cleaning device in a chromatographic column, and the central control unit acquires cleaning frequency according to the last detection result stored in the information storage module to clean the chromatographic column;
and step S3, the central control unit obtains the amount of each impurity of the propylene fumarate tenofovir disoproxil tablet according to the chromatogram of the solution to be detected, wherein the central control unit compares each impurity with the preset amount of each impurity to judge the quality of the current propylene fumarate tenofovir disoproxil tablet medicament.
2. The method for detecting impurity of medicine based on Propofovir fumarate tablets as claimed in claim 1, wherein the central control unit determines the sensitivity of the current detection system according to the signal-to-noise ratio al of the peak height of the principal component in the chromatogram of the sensitivity solution compared with a preset signal-to-noise ratio, wherein,
when AL is less than or equal to AL1, the central control unit judges that the sensitivity of the current detection system does not meet the standard, and adjusts the content of each mobile phase and each elution time in the gradient elution;
when AL1 is more than AL and less than AL2, the central control unit judges that the sensitivity of the current detection system does not meet the standard, and the central control unit starts a cleaning device in the chromatographic column of the detection system to wash the chromatographic column;
when AL is larger than or equal to AL2, the central control unit judges that the sensitivity of the current detection system meets the standard;
the central control unit presets a signal-to-noise ratio AL, sets a first preset signal-to-noise ratio AL1 and a second preset signal-to-noise ratio AL 2.
3. The method for detecting impurities in a medicine based on Propofovir fumarate tablets according to claim 2, wherein when the acquired signal-to-noise ratio of the central control unit is between a first preset signal-to-noise ratio and a second preset signal-to-noise ratio, the central control unit acquires the cleaning frequency of the cleaning device according to the real-time flow fluctuation rate d of each gradient elution stage of the solution to be detected of the last detection data acquired by the sensor to flush the chromatographic column,
when D is less than or equal to D1, the central control unit selects a first cleaning frequency v1 to wash the chromatographic column;
when D1 is more than D and less than D2, the central control unit selects a second cleaning frequency v2 to wash the chromatographic column;
when D is larger than or equal to D2, the central control unit selects a third cleaning frequency v3 to wash the chromatographic column;
the central control unit presets a fluctuation rate D, sets a first preset fluctuation rate D1 and a second preset fluctuation rate D2, presets a cleaning frequency v, and sets a first preset cleaning frequency v1, a second preset cleaning frequency v2 and a third preset cleaning frequency v 3.
4. The method for detecting impurities in a medicine based on Propofovir fumarate tablets as claimed in claim 3, wherein the central control unit obtains real-time flow rate of each gradient elution stage of the solution to be detected to obtain real-time flow fluctuation rate d, and sets d = ((d1-d0)2+(d2-d0)2+···+(dn-d0)2) And/n, wherein d1 is the real-time flow rate obtained by the sensor in the first gradient elution stage, d2 is the real-time flow rate obtained by the sensor in the second gradient elution stage, · · dn is the real-time flow rate obtained by the sensor in the nth gradient elution stage, and d0 is the average value of the real-time flow rates obtained by the sensors from the first gradient elution stage to the nth gradient elution stage, wherein n is the total number of the gradient elution stages.
5. The method of claim 2, wherein the central control unit stores previous detection data through the information storage module, obtains the variation degree b of the correction factor according to the difference between each impurity correction factor and a preset standard value of each impurity correction factor, and sets b = | b1-b10|/b10+ | b2-b20|/b20+ · | -Bk0|/Bk0, wherein b1 is the central control unit obtains the first impurity correction factor, b2 is the central control unit obtains the second impurity correction factor · · Bk is the central control unit obtains the kth impurity correction factor, b10 is the central control unit preset the first impurity correction factor, b20 is the central control unit preset the second impurity correction factor standard value · Bk0 is the central control unit preset the standard value of the central control factor, k is set as the total number of impurities.
6. The method for detecting impurity of medicine based on Propofovir fumarate tablets as claimed in claim 5, wherein the central control unit obtains the correction factor variation degree B to compare with the preset variation degree B, and adjusts the selected cleaning frequency vp, wherein,
when B is not more than B1, the central control unit does not adjust the selected cleaning frequency;
when B1 < B < B2, the central control unit reduces the selected cleaning frequency vp to vp1, and sets vp1= vp x (1- (B-B1) x (B2-B)/(B1 x B2));
when B is larger than or equal to B2, the central control unit increases the selected cleaning frequency vp to vp2, and sets vp2= vp x (1+ (B-B2)/B2);
the central control unit presets a change degree B, sets a first preset change degree B1 and a second preset change degree B2, and p =1,2 and 3.
7. The method for detecting impurity of medicine based on Propofovir fumarate tablets as claimed in claim 6, wherein the cleaning device comprises a sliding mechanism, a rotating mechanism disposed on the sliding mechanism and a spraying mechanism connected with the rotating mechanism, the central control unit presets a cleaning frequency V, and the central control unit adjusts the sliding rate of the sliding mechanism and the rotating rate of the rotating mechanism of the cleaning device according to the comparison between the acquired cleaning frequency vpq of the cleaning device and the preset cleaning frequency, wherein,
when vpq is less than or equal to V1, the central control unit reduces the rotation speed vz of the rotating mechanism to vz1 and reduces the sliding speed vh of the sliding mechanism to vh 1;
when V1 < vpq < V2, the central control unit increases the rotation speed vz of the rotating mechanism by vz 2;
when vpq is larger than or equal to V2, the central control unit increases the rotation speed vz of the rotating mechanism to vz3 and increases the sliding speed vh of the sliding mechanism to vh 2;
the central control unit presets a cleaning frequency V, sets a first preset cleaning frequency V1, and sets a second preset cleaning frequency V2, q =1, 2.
8. The method for detecting pharmaceutical impurities based on Propofovir fumarate tablets according to claim 7, wherein the central control unit obtains the washing frequency vpq of the washing device at or below a first preset washing frequency V1, the central control unit reduces the rotation speed vz of the rotating mechanism by vz1, sets vz1= vz x (1- (V1-vpq)/V1), reduces the sliding speed vh of the sliding mechanism to vh1, sets vh1= vh x (1- (V1-vpq)/V1, the central control unit obtains the washing frequency vpq of the washing device between the first preset washing frequency V1 and a second preset washing frequency V2, the central control unit increases the rotation speed vz of the rotating mechanism by vz2, sets vz2= vz x (1+ (V82 2-vpq)/(V vpq-V1)/(V vpq-V86 1)), the central control unit increases the rotational speed vz of the rotational mechanism by vz3, sets vz3= vz × (1+ (vpq-V2)/V2), increases the sliding speed vh of the sliding mechanism to vh2, and sets vh2= vh × (1+ (vpq-V2)/V2).
9. The method for detecting the pharmaceutical impurities based on the Propofovir fumarate tablets according to claim 2, wherein the signal-to-noise ratio of the main component peak height in the chromatogram of the sensitivity solution obtained by the central control unit is less than or equal to a first preset signal-to-noise ratio, the central control unit determines that the sensitivity of the current detection system does not meet the standard, and the central control unit adjusts the content of the mobile phase in each stage of the gradient elution according to the last detection data by using the obtained tailing factor Ti of each peak and a preset ith peak tailing factor Ti0, wherein,
when Ti is less than or equal to Ti0, the central control unit obtains the separation degree to adjust the elution time of each gradient stage;
when Ti is more than Ti0, the central control unit reduces the ratio of the first mobile phase to the second mobile phase in the i-stage gradient elution to Gi1, and sets Gil = Gi x (1- (Ti-Ti0)/Ti0), wherein the content of the first mobile phase mi1 in the i-stage gradient elution is adjusted to mi1, mi11= mi1/Gi × Gil, the content of the second mobile phase mi2 in the i-stage gradient elution is adjusted to mi21, and mi21=100-mi11;
wherein i =1,2 · n.
10. The method for detecting impurity of medicine based on Propofovir fumarate tablets as claimed in claim 9, wherein the central control unit adjusts the gradient elution time of the i-th stage according to the comparison of the separation degree ti of adjacent peaks of the previous detection data with a preset separation degree standard value, wherein,
when ti is less than or equal to W0, the central control unit increases the elution time ei to ei1 in the i-stage gradient stage, and sets ei1= ei x (1+ (W0-ti)/W0);
when ti > W0, the central control unit shortened the i-th stage gradient elution time ei to ei2, setting ei2= ei x (1- (ti-W0)/W0).
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