CN113671083A - Method for splitting prulifloxacin enantiomer - Google Patents
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Abstract
The invention belongs to the technical field of pharmacy, and particularly relates to a method for splitting an enantiomer of prulifloxacin. The resolution method adopts a chiral coordination exchange mobile phase additive HLPC method, chiral additives are added into a mobile phase, and are coordinated with the prulifloxacin enantiomer to form a ternary complex of two diastereomers, and then the enantiomer is resolved on a chromatographic column of a non-chiral stationary phase; the method comprises the following specific steps: (1) preparation of sample liquid, and (2) resolution step and conditions. The method for separating the enantiomer of prulifloxacin by using the chiral coordination exchange mobile phase additive HLPC method is successfully established, is simple to operate, economical and practical, has good linear relation, precision and sensitivity, and can be used for separating and controlling the quality of the enantiomer of prulifloxacin.
Description
Technical Field
The invention belongs to the technical field of pharmacy, and particularly relates to a method for splitting an enantiomer of prulifloxacin.
Background
The chirality of drug molecules has close relationship with the pharmacological activity, toxicity and pharmacokinetic properties of the drug. When the enantiomers of chiral drugs enter into the body, they are recognized and matched as different molecules, so that the enantiomers have stereoselectivity in pharmacodynamics, pharmacokinetics and toxicology, so that the biological activity, metabolic process and toxicity of the enantiomers may be obviously different, and the most typical example is the 'reaction stop' event in the last 60 th century. In view of the difference in pharmacological activity and toxicity of enantiomers of chiral compounds, it is very necessary and significant to develop studies on enantiomer chemistry (purity identification, examination, etc.), pharmacology, toxicology, clinical application, etc., however, to develop these works, the problem of enantiomer resolution must be solved first, and the establishment of a chiral separation analysis method becomes a key part in the development of chiral drug research.
Prulifloxacin (Prulifloxacin) is a fourth-generation quinolone broad-spectrum antibiotic developed and researched by Nippon New drug company, has wide bactericidal and bacteriostatic effects on gram-negative and positive bacteria, anaerobic bacteria, chlamydia, mycoplasma and the like, and is mainly used for respiratory tract infection, urinary tract infection and skin soft tissue infection clinically. The molecular structure of prulifloxacin has a chiral carbon, and it has been reported that levo-prulifloxacin and physiologically acceptable salts thereof can replace the existing antibacterial agent prulifloxacin and physiologically acceptable salts thereof, and not only the antibacterial action is obviously enhanced, but also the toxicity is small. In order to know the proportion of the levo-prulifloxacin in the medicine, a corresponding enantiomer separation method is necessary to be established, but the enantiomer separation report of the medicine is almost unavailable at home and abroad.
The structural formula of the prulifloxacin enantiomer is as follows:
disclosure of Invention
The invention aims to provide a method for splitting an enantiomer of prulifloxacin, successfully establishes a method for splitting the enantiomer of prulifloxacin by using a chiral coordination exchange mobile phase additive HLPC method, has the advantages of simple operation, economy and practicability, and good linear relation, precision and sensitivity, and can be used for splitting and quality control of the enantiomer of prulifloxacin.
The invention provides a method for splitting an enantiomer of prulifloxacin, which adopts a chiral coordination exchange mobile phase additive HLPC method, adds a chiral additive in a mobile phase, coordinates with the enantiomer of prulifloxacin to form a ternary complex of two diastereomers, and then splits the enantiomer on a chromatographic column of a non-chiral stationary phase; the method comprises the following specific steps:
(1) preparing a sample solution: weighing a prulifloxacin reference substance or raw material, adding acetonitrile to dissolve and dilute the prulifloxacin reference substance or raw material to obtain a sample solution of the reference substance or raw material;
(2) splitting step and conditions: preparing a chiral additive solution containing L-isoleucine and copper sulfate, adjusting the pH to 3.2-3.5 by using a sodium hydroxide or phosphoric acid solution, mixing the solution with methanol to be used as a mobile phase, resolving the sample solution in the step (1) by using a C18 chromatographic column, and detecting at the wavelength of 273-279 nm.
In the technical scheme, the chiral coordination exchange mobile phase additive HLPC method is adopted to split the prulifloxacin enantiomer, a wider variable range can be provided, parameters such as chiral ligand type, concentration, mobile phase pH and the like can be changed, and analysis can be carried out by using a conventional liquid phase and a conventional chromatographic column; acetonitrile is used for dissolving and diluting a sample, and prulifloxacin in the obtained sample is stable, so that the detection of the sample is facilitated, and the error is small; the L-isoleucine is used as chiral amino acid to realize the resolution of the prulifloxacin enantiomer, and the separation degree is good. Specifically, L-isoleucine may be replaced with L-phenylalanine.
Further, in the step (1) of the technical scheme, the sample solution is prepared by weighing a prulifloxacin reference substance or raw material, adding acetonitrile to dissolve the prulifloxacin reference substance or raw material, then adding a mobile phase to dilute the solution to obtain a sample solution of the reference substance or raw material, and storing the sample solution at 4 ℃. In the technical scheme, the sample solution is diluted by the mobile phase, so that the sample volume is not particularly required, the separation degree is good, the stability is relatively poor, the sample solution needs to be prepared and used at the present, and the sample solution is stored at low temperature.
Further, in the step (2) of the technical scheme, the volume ratio of the chiral additive solution to the methanol in the mobile phase is 65-70: 30-35.
Further, in the step (2) of the above technical scheme, the pH is adjusted to 3.5.
The pH of the mobile phase has great influence on the resolution, the mobile phase is alkaline and is favorable for the formation of a complex, generally, the alkaline mobile phase obtains higher capacity factor and separation degree compared with the alkaline mobile phase, but the copper ion complex precipitation speed of the mobile phase is obviously accelerated after the pH is more than 3.5, and the research cannot be carried out, so the acidic mobile phase with the pH of 3.2-3.5, preferably 3.5, is adopted in the technical scheme.
Further, in the step (2) of the technical scheme, the concentration of the L-isoleucine in the chiral additive solution is 8-12 mmol/L. The increase of the concentration of the L-isoleucine can increase the concentration of the binary complex of the L-isoleucine and the copper ions in the mobile phase, can generate more binary complexes in the mobile phase for distribution on a chromatographic column stationary phase, and can improve the separation degree between peaks of the enantiomers of the prulifloxacin.
Further, the concentration of L-isoleucine in the chiral additive solution in the above technical scheme is 8 mmol/L.
Further, the copper ion concentration of the copper sulfate solution in the chiral additive solution is 3-5 mmol/L.
Further, the copper ion concentration of the copper sulfate solution in the chiral additive solution is 4 mmol/L.
Furthermore, in the step (2) of the above technical solution, the chromatographic column is Asahi Ultimate XB-C18, and the specification is 4.6mm × 250mm, 5 μm.
Furthermore, in the step (2) of the technical scheme, the sample injection amount is 2-10 μ L.
Compared with the prior art, the method has the beneficial effects that:
the method for separating the enantiomer of the prulifloxacin by using the chiral coordination exchange mobile phase additive HLPC method is successfully established, is simple to operate, is economical and practical, has good linear relation, precision and sensitivity, and can be used for separating and controlling the quality of the enantiomer of the prulifloxacin.
Drawings
FIG. 1 is a chromatogram of a control sample of prulifloxacin, wherein A is a solution d, and the sample amount is 10 μ L; b is solution a, the sample injection amount is 2 mu L; c is solution b, the sample amount is 10 mu L;
FIG. 2 is a wavelength chromatogram for detecting prulifloxacin according to the present invention;
FIG. 3 is a chromatogram of a reference of prulifloxacin with acetonitrile as the organic phase according to the present invention.
Detailed Description
The technical features of the present invention described above and those described in detail below (as an embodiment) can be combined with each other to form a new or preferred technical solution, but the present invention is not limited to these embodiments, and the embodiments also do not limit the present invention in any way.
The experimental procedures in the following examples are conventional unless otherwise specified. The formulations according to the following examples are all commercially available products and are commercially available, unless otherwise specified.
The invention is described in further detail below with reference to the figures and examples:
the experimental reagent and the detection method comprise the following steps:
1. instruments and reagents
1.1 Instrument: LC-20AD XR high performance liquid chromatograph (shimadzu, japan), MS205DU electronic balance (mettler-toledo, switzerland);
1.2 reagent: prulifloxacin control [ echeie (shanghai) chemical industry development limited, lot no: XM8QF-TS, content: 98.0 percent, a reference substance is racemate, the content of single enantiomer is 49.0 percent, L-phenylalanine, L-isoleucine and L-proline are biochemical reagents, methanol and acetonitrile are chromatographic pure, water is ultrapure water, and other reagents are analytical pure.
2. Solution preparation
Weighing 105.32mg of prulifloxacin reference substance, placing in a 100mL measuring flask, adding acetonitrile to dissolve and dilute to scale, shaking up to obtain reference substance stock solution (containing 1032.1 μ g/mL of prulifloxacin, solution a); taking 2mL of the solution, placing the solution into a 10mL measuring flask, adding acetonitrile to dissolve and dilute the solution to a scale, and shaking up the solution to be used as a reference sample solution I (containing 206.4 mu g/mL of prulifloxacin and solution b).
Weighing 102.12mg of prulifloxacin reference substance, placing in a 100mL measuring flask, adding 20mL of acetonitrile for dissolving, adding a mobile phase for diluting to a scale, and shaking up to obtain a solution c containing 1000.8 mug/mL of prulifloxacin; taking 2mL of the solution, placing the solution in a 10mL measuring flask, adding a mobile phase to dilute the solution to a scale, shaking the solution uniformly to obtain a second reference sample solution (containing 200.2 mu g/mL of prulifloxacin, newly prepared, stored at 4 ℃ and solution d).
3. Chromatographic conditions
A chromatographic column: asahi Ultimate XB-C18(4.6 mm. times.250 mm, 5 μm); mobile phase: l-isoleucine-copper sulfate solution (containing 8 mmol/L-isoleucine and 4mmol/L copper sulfate, pH adjusted to 3.5 with sodium hydroxide or phosphoric acid solution) -methanol (68/32, V/V); flow rate: 1.0 mL/min; the column temperature is 40 ℃; detection wavelength: 276 nm; injector sample pan temperature: 4 ℃ is prepared.
Example 1: effect of Diluent and sample volume on resolution
Taking acetonitrile as a reference sample solution I (solution b) with the diluent concentration of 206.4 mu g/mL, when the injection volume is 10 mu L, the peak types of two enantiomers of the prulifloxacin are particularly poor, the number of theoretical plates and the separation degree are not satisfactory, and a larger solvent peak is generated. Taking a reference substance stock solution (solution a) with acetonitrile as a diluent with the concentration of 1032.1 mu g/mL and a reference substance sample solution II (solution d) with the mobile phase as a diluent with the concentration of 200.2 mu g/mL, respectively injecting 2 mu L and 10 mu L, injecting the two modes with the separation degree between two enantiomer peaks of prulifloxacin of about 3.61 and 3.78, wherein the prulifloxacin peaks have almost no difference, but the solvent peak is larger when the acetonitrile is used as the diluent, and the chromatogram is shown in figure 1.
Therefore, when the sample injection volume of the acetonitrile-diluted reference sample solution is reduced to 2 mu L, the peak type of the prulifloxacin enantiomer can be better improved. Therefore, when the sample solution of the reference substance diluted by acetonitrile is used for analysis, the sampling volume is suitably 2 μ L; when the analysis is performed using the control sample solution diluted with the mobile phase, the amount of the sample to be taken is not particularly limited, and it is preferable that the amount of the sample to be taken is 10. mu.L.
Example 2: effect of diluents on stability
Taking a reference substance stock solution (solution a) which is just prepared and is placed for a period of time and takes acetonitrile as a diluent, wherein the concentration of the reference substance stock solution is 1032.1 mu g/mL, and a reference substance sample solution II (solution d) which takes a mobile phase as a diluent, wherein the concentration of the reference substance sample solution II is 200.2 mu g/mL, carrying out sample injection analysis according to the chromatographic condition of 'experimental reagent and detection method 3', wherein the sample injection volume of the solution a is 2 mu L, and the sample injection volume of the solution d is 10 mu L, and inspecting the stability of the solution.
As a result: the peak areas of the two enantiomers of prulifloxacin after being placed for 3h are reduced by about 2% when diluted by using a mobile phase, and the peak area of the enantiomer of prulifloxacin after being placed for 80h is reduced by less than 0.2% when diluted by using acetonitrile, and the peak areas are almost unchanged.
Therefore, the prulifloxacin diluted by acetonitrile has better stability; whereas prulifloxacin diluted with mobile phase is relatively unstable, and needs to be freshly prepared and stored at 4 ℃.
Example 3: effect of chiral mobile phase additives on resolution
And respectively taking L-phenylalanine, L-isoleucine and L-proline as chiral ligands to carry out resolution analysis on the prulifloxacin enantiomer, wherein a prulifloxacin reference stock solution (solution a) with the concentration of about 1032.1 mu g/mL is selected, and the sample volume is 2 mu L for carrying out experiments.
As a result: when the L-proline is used, the prulifloxacin only has 1 chromatographic peak, and the prulifloxacin enantiomer can not be separated; and when the L-phenylalanine and the L-isoleucine are used, the prulifloxacin in the chromatogram has 2 chromatographic peaks, and the separation of the enantiomer of the prulifloxacin can be realized. The retention time of the prulifloxacin enantiomer was longer when the L-phenylalanine was used for resolution, and the methanol ratio was increased to 36% to examine the separation degree between two enantiomer peaks when the retention time of the prulifloxacin enantiomer was similar, and the results are shown in table 1.
TABLE 1 Effect of different chiral amino acids on Retention time and resolution
As can be seen from the results in Table 1, although both degrees of separation were greater than 3, when L-isoleucine was used, a better degree of separation was obtained, and the effect was better. Therefore, L-isoleucine is preferable.
Example 4: effect of L-isoleucine concentration on resolution
The detection wavelength of prulifloxacin is shown in figure 2 by analysis, and the optimal wavelength is 276 nm. Since L-isoleucine and copper sulfate chiral additives also have ultraviolet absorption at 276nm, and the mobile phase has too large absorption value at 276nm (background absorption) due to too high concentration of L-isoleucine, the peak height and peak area of prulifloxacin enantiomer will be reduced during sample analysis, so that the influence of several different concentrations of L-isoleucine on resolution (wherein, the molar ratio of L-isoleucine and copper sulfate in chiral additive solution is 2: 1) is analyzed, and the results are shown in Table 2 with reference to the method of example 3.
TABLE 2 Effect of L-isoleucine concentration on resolution
As can be seen from the results in Table 2, the peak area of the enantiomer was continuously decreased at the concentration of L-isoleucine of 6-12 mmol/L; however, when the concentration of L-isoleucine was 8mmol/L, not only was the degree of separation better, but also the decrease in peak area was minimal. Therefore, the preferred concentration is 8 mmol/L-isoleucine.
Example 5: effect of Metal ion concentration on resolution
The optimum copper ion concentration was found by keeping the concentration of L-isoleucine constant, i.e., by finding the optimum molar ratio of L-isoleucine to copper ion, several different copper sulfate concentrations were set, and the results are shown in Table 3 with reference to the method of example 3.
TABLE 3 Effect of copper sulfate concentration on resolution
As can be seen from the results of table 3, as the copper ion concentration increases, the enantiomeric peak retention time, the degree of separation, and the peak area all decrease; when the copper ion concentration is 3-5mmol/L, the separation degree between the peaks of the prulifloxacin enantiomers is reduced from 3.7 to 3.4, and the change is relatively small, so that the copper ion concentration is suitable for 3-5 mmol/L.
When the concentration of copper ions is 3mmol/L, the separation degree between peaks of the prulifloxacin enantiomer is increased by only 0.1 compared with that of 4mmol/L, but the analysis time needs to be prolonged to 29 min. Therefore, the copper sulfate concentration is preferably 4 mmol/L.
Example 6: effect of mobile phase pH on resolution
After the pH value of the chiral additive solution is more than 3.5, the generation speed of the copper ion complex is obviously accelerated, so the influence of the change of the pH value of the mobile phase between 3.0 and 3.5 on the resolution is examined, and the mobile phase does not have the copper ion complex precipitation within the pH value range. In this example, the influence of the pH of the chiral additive solution varying between 3.0 and 3.5 on the resolution was examined, and the results are shown in Table 4, referring to the method of example 3.
Table 4 effect of mobile phase pH on retention time and separation
As can be seen from the results in table 4, the greater the pH, the greater the degree of separation between the peaks of the enantiomers of prulifloxacin. Of these, the degree of separation is less than 1.5 at pH 3.0, the two enantiomeric peaks are not completely separated, and the degree of separation is best at pH 3.5. Therefore, a pH of 3.5 is preferred.
Example 7: effect of organic modifiers on resolution
Examining the influence of different organic solvents on the resolution, analyzing by using methanol and acetonitrile as the organic solvents of the mobile phase, and injecting the sample according to the method of example 3, wherein the chromatogram of the prulifloxacin reference of the organic phase with methanol is shown in figure 1, and the chromatogram of the prulifloxacin reference of the organic phase with acetonitrile is shown in figure 3.
As can be seen from fig. 1 and 3, better resolution effect can be obtained by using methanol as the organic phase; and when the organic phase uses acetonitrile, the prulifloxacin enantiomer can not be separated. Therefore, methanol was chosen as the organic phase.
Example 8: methodology investigation
(1) Linear relation
Diluting with appropriate amount of solution c and mobile phase to obtain solution containing Prulifloxacin concentration of about 300, 250, 200, 150, 100, 50, 20, 10 μ g/mL (single enantiomer concentration of Prulifloxacin is 50% of Prulifloxacin concentration, i.e. about 150, 125, 100, 75, 50, 25, 10, 5 μ g/mL), sampling above solutions 10 μ L respectively according to "experimental reagent and detection method 3 chromatographic conditions", and recording chromatogram. Taking the peak area of the single enantiomer of prulifloxacin as the ordinate (y) and the concentration (x) of the single enantiomer of prulifloxacin as the abscissa to perform linear regression.
The result shows that the concentration of the single enantiomer of the prulifloxacin is in a good linear relation with the corresponding peak area between 5 and 150 mu g/mL. The regression equation for enantiomer 1 (pioneer) of prulifloxacin is: 41164.7 x-31178.2, R2 0.9996; the regression equation for enantiomer 2 (posterior) of prulifloxacin is: y is 41277.5 x-27667.5 and R2 is 0.9994.
(2) Precision degree
And taking the solution d, injecting samples for 6 times (10 mu L) respectively according to the chromatographic conditions of the experimental reagent and the detection method 3, and recording a chromatogram. The RSD of the peak area of each enantiomer of prulifloxacin is respectively calculated, and the results are respectively 0.6% (front) and 0.5% (back), which indicates that the precision of the method is good.
(3) Quantitative limit and detection limit
Taking the solution d to be diluted into a solution containing prulifloxacin with the concentration of about 4 mu g/mL and 1.2 mu g/mL (a solution with the single enantiomer with the concentration of about 2 mu g/mL and 0.6 mu g/mL) by a mobile phase, and respectively injecting 10 mu L of the solution in the experimental reagent and detection method 3 chromatographic conditions.
As a result: when the concentration of a single enantiomer of the prulifloxacin is about 2 mu g/mL, the peak signal-to-noise ratio of the enantiomer is more than 10; when the concentration of a single enantiomer of the prulifloxacin is about 0.6 mu g/mL, the peak signal-to-noise ratio of the enantiomer is more than 3. The limits of quantitation and detection of the individual enantiomers of prulifloxacin may be 2 μ g/mL and 0.6 μ g/mL.
In conclusion, the optimal mobile phase composition for separating the prulifloxacin enantiomer, which is obtained by optimizing parameters such as the type and concentration of a ligand, the molar ratio of L-isoleucine to copper ions, pH and the like in the mobile phase, is 8mmol/L L-isoleucine and 4mmol/L copper sulfate solution (pH 3.5) -methanol (68/32, V/V), and the method for separating the prulifloxacin enantiomer by the chiral coordination exchange chromatography mobile phase additive method is successfully established; the method is simple to operate, economical and practical, and has good linear relation, precision and sensitivity; can be used for the resolution and quality control of prulifloxacin enantiomer.
Finally, it should be emphasized that the above-described preferred embodiments of the present invention are merely examples of implementations, rather than limitations, and that many variations and modifications of the invention are possible to those skilled in the art, without departing from the spirit and scope of the invention.
Claims (10)
1. A method for splitting an enantiomer of prulifloxacin is characterized in that a chiral coordination exchange mobile phase additive HLPC method is adopted, a chiral additive is added into a mobile phase, the mobile phase is coordinated with the enantiomer of prulifloxacin to form a ternary complex of two diastereomers, and then the enantiomer is split on a chromatographic column of an achiral stationary phase; the method comprises the following specific steps:
(1) preparing a sample solution: weighing a prulifloxacin reference substance or raw material, adding acetonitrile to dissolve and dilute the prulifloxacin reference substance or raw material to obtain a sample solution of the reference substance or raw material;
(2) splitting step and conditions: preparing a chiral additive solution containing L-isoleucine and copper sulfate, adjusting the pH to 3.2-3.5 by using a sodium hydroxide or phosphoric acid solution, mixing the solution with methanol to be used as a mobile phase, resolving the sample solution in the step (1) by using a C18 chromatographic column, and detecting at the wavelength of 273-279 nm.
2. The method for resolving an enantiomer of prulifloxacin according to claim 1, wherein in the step (1), the sample solution is prepared by weighing prulifloxacin as a reference substance or a raw material, dissolving the prulifloxacin with acetonitrile, diluting with a mobile phase to obtain a sample solution of the reference substance or the raw material, and storing at 4 ℃.
3. The method for resolving an enantiomer of prulifloxacin according to claim 1, wherein in the step (2), the volume ratio of the chiral additive solution to methanol in the mobile phase is 65-70: 30-35.
4. The method for resolving an enantiomer of prulifloxacin according to claim 1, wherein in step (2), the pH is adjusted to 3.5.
5. The method for resolving an enantiomer of prulifloxacin according to claim 1, wherein in the step (2), the concentration of L-isoleucine in the chiral additive solution is 8-12 mmol/L.
6. The method for resolving an enantiomer of prulifloxacin according to claim 5, wherein in the step (2), the concentration of L-isoleucine in the chiral additive solution is 8 mmol/L.
7. The method for resolving an enantiomer of prulifloxacin according to claim 1, wherein in the step (2), the copper ion concentration of the copper sulfate solution in the chiral additive solution is 3-5 mmol/L.
8. The method for resolving an enantiomer of prulifloxacin according to claim 7, wherein in the step (2), the copper ion concentration of the copper sulfate solution in the chiral additive solution is 4 mmol/L.
9. The method for splitting an enantiomer of prulifloxacin according to claim 1, wherein in step (2), the chromatographic column is asahi Ultimate XB-C18 with a specification of 4.6mm x 250mm, 5 μm.
10. The method for resolving an enantiomer of prulifloxacin according to claim 1, wherein in the step (2), the sample volume is 2-10 μ L.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1843335A (en) * | 2006-02-16 | 2006-10-11 | 严洁 | Quisnon dispersion tablet |
| CN103543230A (en) * | 2012-07-09 | 2014-01-29 | 北大方正集团有限公司 | Method for separating and measuring moxifloxacin hydrochloride and enantiomer thereof |
| US20170360881A1 (en) * | 2016-06-17 | 2017-12-21 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| CN111208216A (en) * | 2018-11-21 | 2020-05-29 | 太景生物科技股份有限公司 | Method for separating optical isomers of nemonoxacin or salt thereof |
-
2021
- 2021-08-20 CN CN202110962036.8A patent/CN113671083B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1843335A (en) * | 2006-02-16 | 2006-10-11 | 严洁 | Quisnon dispersion tablet |
| CN103543230A (en) * | 2012-07-09 | 2014-01-29 | 北大方正集团有限公司 | Method for separating and measuring moxifloxacin hydrochloride and enantiomer thereof |
| US20170360881A1 (en) * | 2016-06-17 | 2017-12-21 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| CN111208216A (en) * | 2018-11-21 | 2020-05-29 | 太景生物科技股份有限公司 | Method for separating optical isomers of nemonoxacin or salt thereof |
Non-Patent Citations (4)
| Title |
|---|
| P. RAVISANKAR等: "A VALIDATED RP-HPLC METHOD FOR THE ASSAY OF PRULIFLOXACIN IN MARKETED DRUG PRODUCT USING LEVOFLOXACIN AS AN INTERNAL STANDARD", 《INT. J. CHEM. SCI.》 * |
| 刘学斌等: "高效液相色谱法手性流动相添加剂法拆分尤利沙星对映体", 《药物分析杂志》 * |
| 陈敏等: "高效液相色谱法测定普卢利沙星片的含量", 《药物分析杂志》 * |
| 龙燕等: "高效液相色谱法测定普利沙星片含量及有关物质", 《医药导报》 * |
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