CN109632921A - The detection method of right Ofloxacin content, the electrochemical sensor used and chiral azole compounds in lavo-ofloxacin bulk pharmaceutical chemicals - Google Patents
The detection method of right Ofloxacin content, the electrochemical sensor used and chiral azole compounds in lavo-ofloxacin bulk pharmaceutical chemicals Download PDFInfo
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Abstract
The present invention provides the electrochemical detection method of right Ofloxacin content in a kind of lavo-ofloxacin bulk pharmaceutical chemicals, used in the method chiral polypyrrole electrochemical sensor and chiral azole compounds.With 2,5- dimethoxy-tetrahydrofuran and (R)-(+) -4- methoxy-alpha-methyl benzylamine are raw material, and new chiral azole compounds (R)-(+) -2- (4- methoxyphenyl) -2- (1- pyrrole radicals) ethane is prepared；Then, it using (R)-(+) -2- (4- methoxyphenyl) -2- (1- pyrrole radicals) ethane as monomer, is modified by electrochemical polymerization method to electrode surface, obtains chiral polypyrrole electrochemical sensor；Finally, using the chiral Recognition function of the chirality polypyrrole electrochemical sensor, in conjunction with right Ofloxacin content in electrochemistry cyclic voltammetric analysis method detection lavo-ofloxacin bulk pharmaceutical chemicals.Electrochemical detection method biggest advantage of the invention is that instrument low cost, easy to operate, detection speed is fast, high sensitivity, and does not discharge waste liquid substantially.
Description
Technical field
The present invention provides a kind of detection method of right Ofloxacin content, right oxygen fluorine especially in lavo-ofloxacin bulk pharmaceutical chemicals
The electrochemical detection method of husky star content, the chirality polypyrrole electrochemical sensor used in the electrochemical detection method, with
And provide a kind of chiral azole compounds.
Background technique
Chiral (Chirality) refers to the characteristic that object cannot be overlapped with its mirror image, the chiral compound with this characteristic
Object is known as a pair of of enantiomter.Chirality plays unique function in life process, in the chiral ring of biosystem complexity
In border, the accurately identifying of chiral molecules can lead to organism and generate different physiological effects, and chiral drug is exactly most typical example
Son.Nineteen fifties, which have shocked global " reaction stops " event, allows people to have a lingering fear so far, research hair later
Existing, in raceme " reaction stops ", only its (R)-isomers has sedation, and its (S)-isomers is then with teratogenesis
Effect.FDA in 2000 proposes that the drug with chiral centre must be listed in the form of individual isomer.Not only curative effect in this way
Definitely, few side effects and quantity is few.
Lavo-ofloxacin (its structural formula is as follows), trade name: cola is than appropriate；Molecular formula: C18H20FN3O4；Chemical name:
The fluoro- 2,3- dihydro-3- methyl-1 0- of (3S)-(-)-9- (4- methyl-1-piperazinyl)-7- oxo-7H- pyrido [1,2,3-
De]-[Isosorbide-5-Nitrae] benzoxazine -6- carboxylic acid is by the third generation Comprecin of Japanese first pharmaceutical factory exploitation.The drug
Since 3 carbon atoms even have chirality there are four different group, wherein lavo-ofloxacin is that the optics of Ofloxacin is living
Property (3S)-isomers, antibacterial activity be its (3R)-isomers (also referred to as right Ofloxacin or enantiomter, below
Referred to as right Ofloxacin) 8-128 times, be 2 times of raceme Ofloxacin, and toxic side effect is small.
Currently, the method about Ofloxacin assay right in lavo-ofloxacin bulk pharmaceutical chemicals is mainly high performance liquid chromatography
Method.But the optical purity of chiral drug is detected with high performance liquid chromatography, generally require expensive chiral chromatographic column or addition
The mobile phase of chiral induction agent, not only testing cost is high in this way, cumbersome, can also generate a large amount of mobile phase waste liquid；Separately
Outside, detection speed is slow, detection time is long, and detection limits low with sensitivity and high performance liquid chromatography shortcoming.
Summary of the invention
In view of the above problems, the present inventor has developed right Ofloxacin in a kind of Electrochemical Detection lavo-ofloxacin bulk pharmaceutical chemicals
The method of content is prepared with 2,5- dimethoxy-tetrahydrofuran and (R)-(+) -4- methoxy-alpha-methyl benzylamine for raw material
New chiral azole compounds (R)-(+) -2- (4- methoxyphenyl) -2- (1- pyrrole radicals) ethane；Then, with (R)-(+)-
2- (4- methoxyphenyl) -2- (1- pyrrole radicals) ethane is monomer, is modified by electrochemical polymerization method to electrode surface, is obtained in one's hands
Property polypyrrole electrochemical sensor；Finally, using the chiral Recognition function of the chirality polypyrrole electrochemical sensor, in conjunction with electrification
Learn right Ofloxacin content in cyclic voltammetric analysis method detection lavo-ofloxacin bulk pharmaceutical chemicals.
Therefore, the purpose of the present invention is to provide a kind of chiral azole compounds；
Another object of the present invention is to provide a kind of chiral polypyrrole electrochemical sensors；
A further purpose of the present invention is to provide a kind of quick, easy to operate, accurate, sensitive lavo-ofloxacin bulk pharmaceutical chemicals
The electrochemical detection method of middle right Ofloxacin content, the detection method utilize the hand of above-mentioned chiral polypyrrole electrochemical sensor
Property identification function containing for right Ofloxacin in lavo-ofloxacin bulk pharmaceutical chemicals can easy, accurately be detected by electrochemical method
Amount.
According to an aspect of the present invention, the present invention provides a kind of new chiral azole compounds (R)-(+) -2- (4- first
Phenyl) -2- (1- pyrrole radicals) ethane, structural formula is as follows:
Ethane preparation method is such as chirality azole compounds (R)-(+) -2- (4- the methoxyphenyl) -2- (1- pyrrole radicals)
Under:
(R)-(+) -4- methoxy-alpha-methyl benzylamine and 2,5- dimethoxy-tetrahydrofuran reaction, obtains (R)-(+) -2-
(4- methoxyphenyl) -2- (1- pyrrole radicals) ethane, reaction equation are as follows:
Under acid catalysis, 2,5- dimethoxy-tetrahydrofurans and (R)-(+) -4- methoxy-alpha-methyl benzylamine are condensed
Reaction, obtains (R)-(+) -2- (4- methoxyphenyl) -2- (1- pyrrole radicals) ethane.
Specifically, in the reaction, 2,5- dimethoxy-tetrahydrofuran and (R)-(+) -4- methoxy-alpha-methyl benzylamine rub
You are than being 5:1~1:1, and preferably 3:1~1:1；Catalyst acid can be dilute sulfuric acid, dilute hydrochloric acid or glacial acetic acid etc., and preferably
Glacial acetic acid；Reaction temperature is 50 DEG C~100 DEG C, and preferably 70 DEG C~80 DEG C；Reaction time is 1~4h, and preferably 2~2.5h.
According to another aspect of the present invention, the present invention provides a kind of chiral polypyrrole electrochemical sensor, chiral poly- pyrrole
Coughing up electrochemical sensor includes: glass-carbon electrode, and modifies poly- [(R)-(+) -2- (4- methoxyphenyl)-on glass-carbon electrode
2- (1- pyrrole radicals) ethane] film layer.
Chirality polypyrrole electrochemical sensor according to the present invention, is prepared as follows:
Using electrochemical workstation, using glass-carbon electrode as working electrode, platinum electrode is to electrode, and Ag/AgCl electrode is
Reference electrode；(R)-(+) -2- (4- methoxyphenyl) -2- (1- pyrrole radicals) ethane, tetrabutylammonium perchlorate and (D)-are dissolved
The acetonitrile solution of (+)-camphor -10- sulfonic acid is electrolyte；Above three electrode is inserted into electrolyte and constitutes three electrode of a Room
System；By cyclic voltammetry, (R)-(+) -2- (4- methoxyphenyl) -2- (1- pyrrole radicals) ethane is poly- in glassy carbon electrode surface
It closes, obtains poly- [(R)-(+) -2- (4- methoxyphenyl) -2- (1- pyrrole radicals) ethane] film modified glass-carbon electrode, i.e., it is chiral poly-
Pyrroles's electrochemical sensor.
More specifically, the electrochemical workstation is the electrochemical analyser controlled by computer, commercially available can obtain, example
Such as the RST5000 type electrochemical workstation of Suzhou Rui Sitai Instrument Ltd..
Electrode pretreatment is carried out first, and choosing area is about 10~30mm2Glass-carbon electrode, by glass-carbon electrode Al2O3Powder
End (such as 0.05 μm of Al2O3Powder) it is polished, then by glass-carbon electrode, platinum electrode and Ag/AgCl electrode secondary water
Ultrasonic cleaning (such as being cleaned by ultrasonic 5 minutes) cleans (such as being cleaned by ultrasonic 5 minutes) with EtOH Sonicate, then ultrasonic with secondary water
Cleaning (such as being cleaned by ultrasonic 5 minutes).
Then electrolyte quota is carried out, by (R)-(+) -2- (4- methoxyphenyl) -2- (1- pyrrole radicals) ethane, the tetrabutyl
Ammonium perchlorate and (D)-(+)-camphor -10- sulfonic acid are added in acetonitrile, accelerate to dissolve with ultrasonic wave, lead to nitrogen deoxygenation, be electrolysed
Liquid, wherein the concentration of (R)-(+) -2- (4- methoxyphenyl) -2- (1- pyrrole radicals) ethane is 0.05~0.2mol/L, preferably
0.09~0.12mol/L；The concentration of tetrabutylammonium perchlorate is 0.05~0.2mol/L, preferably 0.09~0.12mol/L；
(D)-(+)-concentration of camphor -10- sulfonic acid is 0.05~0.2mol/L, preferably 0.09~0.12mol/L.
Pretreated glass-carbon electrode, platinum electrode and Ag/AgCl electrode are inserted into structure in the electrolyte of above-mentioned preparation
At a Room three-electrode system, preferably in a nitrogen atmosphere using cyclic voltammetry carry out electrochemical polymerization, electric potential scanning range be-
0.2~2.0V, scanning speed 0.05V/s, circulating ring number are 30~100 circles, preferably 40~60 circles, (R)-(+) -2- (4- methoxy
Base phenyl) -2- (1- pyrrole radicals) ethane glassy carbon electrode surface polymerize, obtain poly- [(R)-(+) -2- (4- methoxyphenyl) -2-
(1- pyrrole radicals) ethane] film modified glass-carbon electrode, i.e., chiral polypyrrole electrochemical sensor.
It is according to the present invention also on the one hand, a kind of electrochemistry of right Ofloxacin content in lavo-ofloxacin bulk pharmaceutical chemicals is provided
Detection method.Since lavo-ofloxacin and right Ofloxacin have different three-dimensional structures, and the chirality polypyrrole is electrochemical
Learning sensor has three-dimensional structure identification function, when lavo-ofloxacin and right Ofloxacin are including chiral polypyrrole electrification
When learning generation redox reaction in the electrochemical system of sensor, respective oxidation peak is respectively appeared at different current potentials.
Then it can convert according to right Ofloxacin oxidation peak current numerical value and obtain right Ofloxacin concentration.
Specifically, the above-mentioned chiral polypyrrole electrochemical sensor being prepared and Ag/AgCl reference electrode are inserted into
In lavo-ofloxacin standard solution, saturated calomel electrode is inserted into saturated potassium chloride solution, in lavo-ofloxacin standard solution and
Salt bridge is built between saturated potassium chloride solution, is then connected the electrodes on electrochemical workstation, and cyclic voltammetry is used under room temperature
It is detected, setting electric potential scanning range is -0.2~2.4V, and scanning speed 0.1V/s, circulating ring number is 1 circle, measures a left side
Ofloxacin has a oxidation peak at 1.589V, and wherein lavo-ofloxacin standard solution is dissolved in for lavo-ofloxacin standard items and contains
It prepares and obtains in the acetonitrile solution of tetrabutylammonium perchlorate.Using above-mentioned same method, measures right Ofloxacin and exist
There is an oxidation peak at 1.973V.The oxidation peak of lavo-ofloxacin and right Ofloxacin is present in different current potentials, i.e. the hand
Property polypyrrole electrochemical sensor can identify lavo-ofloxacin and right Ofloxacin.
The electrochemical detection method of right Ofloxacin content in lavo-ofloxacin bulk pharmaceutical chemicals of the invention, steps are as follows:
Step 1: drawing standard curve and establish equation of linear regression
Solution is prepared
Placebo solution: being added tetrabutylammonium perchlorate in acetonitrile, be prepared into containing tetrabutylammonium perchlorate 0.05~
The acetonitrile solution of 0.2mol/L；
Standard solution: taking above-mentioned placebo solution, and right Ofloxacin standard items are added thereto, and series of concentrations is made
Right Ofloxacin standard solution (and preferred concentration is between 1mmol/L~0.05mmol/L)；
It is husky that the above-mentioned chiral polypyrrole electrochemical sensor being prepared and Ag/AgCl reference electrode are inserted into right oxygen fluorine
In star standard solution, saturated calomel electrode is inserted into saturated potassium chloride solution, in right Ofloxacin standard solution and saturation chlorination
Salt bridge is built between potassium solution, is then connected the electrodes on electrochemical workstation, is detected under room temperature using cyclic voltammetry,
The right Ofloxacin standard solution for detecting multiple serial various concentrations respectively, obtains the oxidation of the right Ofloxacin standard solution of each concentration
Peak current numerical value is drawn right Ofloxacin concentration-current standard curve according to the concentration of peak current numerical value and standard solution, is obtained
Equation of linear regression；
Step 2: the Electrochemical Detection of right Ofloxacin content in lavo-ofloxacin bulk pharmaceutical chemicals
Precision weighs lavo-ofloxacin bulk pharmaceutical chemicals, is dissolved in above-mentioned placebo solution, is configured to detection liquid, will be above-mentioned
The chiral polypyrrole electrochemical sensor and Ag/AgCl reference electrode of preparation are inserted into the detection liquid, and saturated calomel electrode is inserted
Enter in saturated potassium chloride solution, builds salt bridge between detection liquid and saturated potassium chloride solution, then connect the electrodes to electrochemistry
On work station, is detected under room temperature using cyclic voltammetry, record right Ofloxacin oxidation peak current numerical value, bring into above-mentioned time
Return equation, calculates the content of right Ofloxacin in the lavo-ofloxacin bulk pharmaceutical chemicals.
It in detection method, is detected under room temperature using cyclic voltammetry, specifically, electric potential scanning model is set
It encloses for -0.2~2.4V, scanning speed 0.1V/s, circulating ring number is 1 circle.
Beneficial effect
Detection method of the invention compared with the existing technology the utility model has the advantages that compare common high performance liquid chromatography, electricity
Chemical detection method biggest advantage is that instrument low cost, easy to operate, detection speed is fast, high sensitivity, and substantially not
Discharge waste liquid.
Detailed description of the invention
Fig. 1 is to draw right Ofloxacin concentration-current standard song according to the concentration of peak current and standard solution in embodiment 3
Line.
Specific embodiment
In the following, further illustrating chiral azole compounds of the invention by embodiment, chiral polypyrrole electrochemistry passes
The electrochemical detection method of right Ofloxacin content in the preparation of sensor and lavo-ofloxacin bulk pharmaceutical chemicals, but guarantor of the invention
Shield range is not limited in these embodiments.
Embodiment 1
(R)-(+) preparation of -2- (4- methoxyphenyl) -2- (1- pyrrole radicals) ethane
Addition 20mL water, 2.00g (0.024mol) sodium acetate dissolve at room temperature in 100mL three-necked bottle, put up reflux
Condenser pipe and agitating device；Add 10mL (0.17mol) glacial acetic acid and 1.208g (0.008mol) (R)-(+) -4- methoxy
Base-Alpha-Methyl benzylamine is warming up to 75 DEG C of stirring 10min；It will be dissolved with 1.5mL (0.012mol) 2,5- dimethoxy-tetrahydrofuran
It is added drop-wise in reaction solution with the aqueous solution of 0.5g (0.006mol) anhydrous sodium acetate, drop finishes, and is maintained at 75 DEG C and stirs 2h, stops
Reaction；Reaction solution is cooled to room temperature, is extracted with dichloromethane, organic phase is taken, is successively washed with water and saturated sodium chloride solution,
It is dry that anhydrous magnesium sulfate is added, which carries out silica gel column chromatography purifying, and eluent is ethyl acetate: petroleum ether=1:19
(volume ratio), obtains target product (R)-(+) -2- (4- methoxyphenyl) -2- (1- pyrrole radicals) ethane 1.1078g, and yield is
68.89%.
Specific rotatory power :+4.1 °；
1H-NMR(DMSO-d6, δ ppm): 1.811-1.828 (d, 3H ,-CH3, J=6.8Hz), 3.795 (s, 3H ,-
OCH3), 5.221-5.274 (q, 1H ,-CH-, J=21.2Hz), 6.190-6.194 (t, 2H, pyrrole ring hydrogen, J=1.6Hz),
6.745-6.755 (t, 2H, pyrrole ring hydrogen, J=4.0Hz), 6.844-6.866 (dd, 2H, phenyl ring hydrogen, J1=2.0Hz, J2=
2.0Hz), 7.050-7.071 (dd, 2H, phenyl ring hydrogen, J1=1.6Hz, J2=1.6Hz)；
13C-NMR(DMSO-d6, δ ppm): 21.75,55.02,56.80,108.12,114.19,119.34,127.48,
136.01,158.45；
HRMS:C13H15NO[M+H]+Calculated value 202.1264, measured value 202.1257.
Embodiment 2
The preparation of chiral polypyrrole electrochemical sensor
Step 1: electrode pretreatment
By glass-carbon electrode with 0.05 μm of Al2O3Powder is polished, by glass-carbon electrode, platinum electrode and Ag/AgCl electricity
Pole secondary water is cleaned by ultrasonic 5 minutes, then EtOH Sonicate cleans 5 minutes, then secondary water is cleaned by ultrasonic 5 minutes.
Step 2: preparing chiral polypyrrole electrochemical sensor
(R)-(+) -2- (4- methoxyphenyl) -2- (1- pyrrole radicals) the ethane 1.005g for taking above-described embodiment 1 to prepare
(0.005mol), tetrabutylammonium perchlorate 1.709g (0.005mol), (D)-(+)-camphor -10- sulfonic acid 1.1615g
(0.005mol) is dissolved in 50mL acetonitrile, is accelerated to dissolve using ultrasonic wave, is led to nitrogen deoxygenation, obtain electrolyte；Using electrochemistry
Work station, using glass-carbon electrode as working electrode, platinum electrode is to electrode, and Ag/AgCl is reference electrode, by above-mentioned pretreatment
Three electrodes crossed are inserted into above-mentioned electrolyte, are constituted a Room three-electrode system, are carried out electrochemical polymerization at normal temperature；Using following
Ring voltammetry, setting electric potential scanning range are -0.2~2.0V, and scanning speed 0.05V/s, circulating ring number is 50 circles, is caused
The film modified glass-carbon electrode of close poly- [(R)-(+) -2- (4- methoxyphenyl) -2- (1- pyrrole radicals) ethane], the i.e. chirality are poly-
Pyrroles's electrochemical sensor.
Embodiment 3
The Electrochemical Detection of right Ofloxacin content in lavo-ofloxacin bulk pharmaceutical chemicals
1. solution is prepared
Placebo solution: being added tetrabutylammonium perchlorate in acetonitrile, is prepared into 0.1mol/ containing tetrabutylammonium perchlorate
The acetonitrile solution of L.
Standard solution:
The above-mentioned placebo solution of 30mL is taken, the right Ofloxacin standard items of 0.05mmol are added thereto, sonic oscillation is molten
Solution, is settled to 50mL with above-mentioned blank control liquid, and the right Ofloxacin standard solution of 1mmol/L is made；
1mmol/L lavo-ofloxacin standard solution is prepared with method；
The above-mentioned placebo solution of 30ml is taken, the right Ofloxacin standard items of 0.025mmol are added thereto, sonic oscillation is molten
Solution, is settled to 50mL with above-mentioned blank control liquid, and the right Ofloxacin standard solution of 0.5mmol/L is made.
The above-mentioned placebo solution of 30ml is taken, the right Ofloxacin standard items of 0.0125mmol, sonic oscillation are added thereto
Dissolution, is settled to 50mL with above-mentioned blank control liquid, and the right Ofloxacin standard solution of 0.25mmol/L is made；
The above-mentioned placebo solution of 30ml is taken, the right Ofloxacin standard items of 0.00625mmol, sonic oscillation are added thereto
Dissolution, is settled to 50mL with above-mentioned blank control liquid, and 0.125mmol/L standard solution is made；
The above-mentioned placebo solution of 30ml is taken, the right Ofloxacin standard items of 0.003125mmol, ultrasound vibration are added thereto
Dissolution is swung, is settled to 50mL with above-mentioned blank control liquid, the right Ofloxacin standard solution of 0.0625mmol/L is made.
2. lavo-ofloxacin and right Ofloxacin oxidation peak position determine
The chiral polypyrrole electrochemical sensor and Ag/AgCl reference electrode that are prepared in embodiment 2 are inserted into
In 1mmol/L lavo-ofloxacin standard solution, saturated calomel electrode is inserted into saturated potassium chloride solution, in lavo-ofloxacin standard
Salt bridge is built between solution and saturated potassium chloride solution, is then connected the electrodes on electrochemical workstation, using circulation under room temperature
Voltammetry is detected, and setting electric potential scanning range is -0.2~2.4V, and scanning speed 0.1V/s, circulating ring number is 1 circle,
Measure lavo-ofloxacin standard solution has a oxidation peak at 1.589V.Using above-mentioned same method, right Ofloxacin is measured
There is an oxidation peak at 1.973V.It is indicated above that the chirality polypyrrole electrochemical sensor can identify lavo-ofloxacin and
Its right Ofloxacin.
3. drawing standard curve and establishing equation of linear regression
The chiral polypyrrole electrochemical sensor and Ag/AgCl reference electrode that are prepared in embodiment 2 are inserted into the right side
In Ofloxacin standard solution, saturated calomel electrode is inserted into saturated potassium chloride solution, in right Ofloxacin standard solution and is satisfied
Build salt bridge between Klorvess Liquid, then connect the electrodes on electrochemical workstation, under room temperature using cyclic voltammetry into
Row detection, setting electric potential scanning range are -0.2~2.4V, and scanning speed 0.1V/s, circulating ring number is 1 circle.Respectively in detection
The right Ofloxacin standard solution of five various concentrations is stated, oxidation peak of the right Ofloxacin standard solution of each concentration at 1.973V is obtained
Current values (referring to following table 1) draw right Ofloxacin concentration-electric current mark according to the concentration of peak current numerical value and standard solution
Directrix curve (referring to Fig. 1), obtaining equation of linear regression is Y=0.64611X+0.10683, and calculates coefficient R2=
0.9998。
Table 1
4. the Electrochemical Detection of right Ofloxacin content in lavo-ofloxacin bulk pharmaceutical chemicals
Lavo-ofloxacin bulk pharmaceutical chemicals: commercially available lavo-ofloxacin bulk pharmaceutical chemicals
Solution is detected to prepare:
Precision weighs 3.6137g lavo-ofloxacin bulk pharmaceutical chemicals, and the above-mentioned blank control liquid of 30mL is added, and sonic oscillation dissolves,
And it is settled to 50mL with blank control liquid, detection solution is made.
It is molten that chiral polypyrrole electrochemical sensor and Ag/AgCl reference electrode prepared by embodiment 2 are inserted into the detection
In liquid, saturated calomel electrode is inserted into saturated potassium chloride solution, builds salt bridge between detection solution and saturated potassium chloride solution, so
After connect the electrodes on electrochemical workstation, detected under room temperature using cyclic voltammetry, setting electric potential scanning range is-
0.2~2.4V, scanning speed 0.1V/s, circulating ring number are 1 circle.Measuring the oxidation peak current numerical value at 1.973V is
0.5632mA, bring into right Ofloxacin calibration curve equation calculate the concentration C of right Ofloxacin in the detection liquid=
0.7063mmol/L, then, the content of right Ofloxacin is 12.762mg in the 3.6137g lavo-ofloxacin bulk pharmaceutical chemicals；Then, should
The content of right Ofloxacin is 3531.6mg/kg in lavo-ofloxacin bulk pharmaceutical chemicals.
Embodiment 4-7
It to the lavo-ofloxacin bulk pharmaceutical chemicals that different manufacturers are bought, is detected according to the method for embodiment 3, as a result such as following table
Shown in 2:
The lavo-ofloxacin bulk pharmaceutical chemicals testing result that 2 different manufacturers of table are bought
| Sample number into spectrum | Right Ofloxacin content (mg/kg) | |
| Embodiment 3 | 1 | 3531.6 |
| Embodiment 4 | 2 | 5188.4 |
| Embodiment 5 | 3 | 3162.9 |
| Embodiment 6 | 4 | 4170.7 |
| Embodiment 7 | 5 | 5149.2 |
Test example
Recovery of standard addition
The accuracy of detection method of the invention is investigated: three mark-on levels be respectively 0.1mmol/L,
0.2mmol/L, 0.3mmol/L, the sample of each level have carried out 3 measurements, calculate each addition according to measured quantity and scalar quantity
The horizontal rate of recovery and precision.As a result table 3 is seen below.
3 detection method of table investigates result
The average recovery rate 99.35%-99.74% of three mark-on levels of right Ofloxacin, method detection limit 0.01ppm,
Illustrate that the measurement result of this method is reliable.
Claims (10)
1. chiral azole compounds (R)-(+) -2- (4- methoxyphenyl) -2- (1- pyrrole radicals) ethane, structural formula are as follows:
2. a kind of preparation method of chiral azole compounds described in claim 1, comprising: under acid catalysis, 2,5- dimethoxies
Base tetrahydrofuran and (R)-(+) -4- methoxy-alpha-methyl benzylamine carry out condensation reaction, obtain (R)-(+) -2- (4- methoxybenzene
Base) -2- (1- pyrrole radicals) ethane.
3. the preparation method of chirality azole compounds as claimed in claim 2, characterized in that in the reaction, 2,5- dimethoxies
The molar ratio of base tetrahydrofuran and (R)-(+) -4- methoxy-alpha-methyl benzylamine is 5:1~1:1；Catalyst acid is dilute sulfuric acid, dilute
Hydrochloric acid or glacial acetic acid；Reaction temperature is 50 DEG C~100 DEG C；Reaction time is 1~4h.
4. a kind of chirality polypyrrole electrochemical sensor, comprising: glass-carbon electrode, and modify poly- [(R)-on glass-carbon electrode
(+) -2- (4- methoxyphenyl) -2- (1- pyrrole radicals) ethane] film layer.
5. chirality polypyrrole electrochemical sensor as claimed in claim 4, characterized in that the chirality polypyrrole electrochemistry passes
Sensor is prepared as follows:
Using electrochemical workstation, using glass-carbon electrode as working electrode, platinum electrode is to electrode, and Ag/AgCl electrode is reference
Electrode；(R)-(+) -2- (4- methoxyphenyl) -2- (1- pyrrole radicals) ethane, tetrabutylammonium perchlorate and (D)-(+)-are dissolved
The acetonitrile solution of camphor -10- sulfonic acid is electrolyte；Above three electrode is inserted into electrolyte and constitutes three electrode body of a Room
System；By cyclic voltammetry, (R)-(+) -2- (4- methoxyphenyl) -2- (1- pyrrole radicals) ethane is poly- in glassy carbon electrode surface
It closes, obtains poly- [(R)-(+) -2- (4- methoxyphenyl) -2- (1- pyrrole radicals) ethane] film modified glass-carbon electrode, i.e., it is chiral poly-
Pyrroles's electrochemical sensor.
6. chirality polypyrrole electrochemical sensor as claimed in claim 4, characterized in that the chirality polypyrrole electrochemistry passes
Sensor is prepared as follows:
Electrode pretreatment is carried out first, and selection area is 10~30mm2Glass-carbon electrode, by glass-carbon electrode Al2O3Powder carries out
Glass-carbon electrode, platinum electrode and Ag/AgCl electrode, are then cleaned by ultrasonic with secondary water, are cleaned with EtOH Sonicate, then use by polishing
Secondary water ultrasonic cleaning；
Then electrolyte quota is carried out, by (R)-(+) -2- (4- methoxyphenyl) -2- (1- pyrrole radicals) ethane, the high chlorine of the tetrabutyl
Sour ammonium and (D)-(+)-camphor -10- sulfonic acid are added in acetonitrile, accelerate to dissolve with ultrasonic wave, lead to nitrogen deoxygenation, obtain electrolyte,
Wherein, the concentration of (R)-(+) -2- (4- methoxyphenyl) -2- (1- pyrrole radicals) ethane be 0.05~0.2mol/L, preferably 0.09
~0.12mol/L；The concentration of tetrabutylammonium perchlorate is 0.05~0.2mol/L, preferably 0.09~0.12mol/L；(D)-(+)-
The concentration of camphor -10- sulfonic acid is 0.05~0.2mol/L, preferably 0.09~0.12mol/L；
Pretreated glass-carbon electrode, platinum electrode and Ag/AgCl electrode are inserted into the electrolyte of above-mentioned preparation and constitute one
Room three-electrode system, preferably carries out electrochemical polymerization using cyclic voltammetry in a nitrogen atmosphere, and electric potential scanning range is -0.2
~2.0V, scanning speed 0.05V/s, circulating ring number are 30~100 circles, preferably 40~60 circles, (R)-(+) -2- (4- methoxybenzene
Base) -2- (1- pyrrole radicals) ethane glassy carbon electrode surface polymerize, obtain poly- [(R)-(+) -2- (4- methoxyphenyl) -2- (1-
Pyrrole radicals) ethane] film modified glass-carbon electrode, i.e., chiral polypyrrole electrochemical sensor.
7. the electrochemical detection method of right Ofloxacin content in a kind of lavo-ofloxacin bulk pharmaceutical chemicals, steps are as follows:
Step 1: drawing standard curve and establish equation of linear regression
Solution is prepared
Placebo solution: being added tetrabutylammonium perchlorate in acetonitrile, be prepared into containing tetrabutylammonium perchlorate 0.05~
The acetonitrile solution of 0.2mol/L；
Standard solution: taking above-mentioned placebo solution, and right Ofloxacin standard items are added thereto, and the right oxygen of series of concentrations is made
Flucloxacillin standard solution (and preferred concentration is between 1mmol/L~0.05mmol/L)；
Chiral polypyrrole electrochemical sensor and Ag/AgCl reference electrode described in any one of claim 4-6 are inserted into
In right Ofloxacin standard solution, saturated calomel electrode is inserted into saturated potassium chloride solution, in right Ofloxacin standard solution and
Salt bridge is built between saturated potassium chloride solution, is then connected the electrodes on electrochemical workstation, is examined using cyclic voltammetry
It surveys, detects the right Ofloxacin standard solution of multiple serial various concentrations respectively, obtain the right Ofloxacin standard solution of each concentration
Oxidation peak current numerical value draws right Ofloxacin concentration-current standard curve according to the concentration of peak current numerical value and standard solution,
Obtain equation of linear regression；
Step 2: the Electrochemical Detection of right Ofloxacin content in lavo-ofloxacin bulk pharmaceutical chemicals
Precision weighs lavo-ofloxacin bulk pharmaceutical chemicals, is dissolved in above-mentioned placebo solution, detection solution is configured to, by above-mentioned system
Standby chiral polypyrrole electrochemical sensor and Ag/AgCl reference electrode are inserted into the detection solution, and saturated calomel electrode is inserted
Enter in saturated potassium chloride solution, builds salt bridge between detection solution and saturated potassium chloride solution, then connect the electrodes to electrification
It learns on work station, is detected using cyclic voltammetry, record right Ofloxacin oxidation peak current numerical value, bring above-mentioned recurrence side into
Journey calculates the content of right Ofloxacin in the lavo-ofloxacin bulk pharmaceutical chemicals.
8. electrochemical detection method as claimed in claim 7, characterized in that it is detected under room temperature using cyclic voltammetry,
Setting electric potential scanning range is -0.2~2.4V, and scanning speed 0.1V/s, circulating ring number is 1 circle.
9. electrochemical detection method as claimed in claim 7, characterized in that the step 1 includes:
1. solution is prepared
Placebo solution: being added tetrabutylammonium perchlorate in acetonitrile, is prepared into the 0.1mol/L's containing tetrabutylammonium perchlorate
Acetonitrile solution；
Standard solution:
The above-mentioned placebo solution of 30mL is taken, the right Ofloxacin standard items of 0.05mmol are added thereto, sonic oscillation dissolution is used
Above-mentioned blank control liquid is settled to 50mL, and the right Ofloxacin standard solution of 1mmol/L is made；
1mmol/L lavo-ofloxacin standard solution is prepared with method；
The above-mentioned placebo solution of 30ml is taken, the right Ofloxacin standard items of 0.025mmol are added thereto, sonic oscillation dissolves,
It is settled to 50mL with above-mentioned blank control liquid, the right Ofloxacin standard solution of 0.5mmol/L is made；
The above-mentioned placebo solution of 30ml is taken, the right Ofloxacin standard items of 0.0125mmol are added thereto, sonic oscillation dissolves,
It is settled to 50mL with above-mentioned blank control liquid, the right Ofloxacin standard solution of 0.25mmol/L is made；
The above-mentioned placebo solution of 30ml is taken, the right Ofloxacin standard items of 0.00625mmol are added thereto, sonic oscillation is molten
Solution, is settled to 50mL with above-mentioned blank control liquid, and 0.125mmol/L standard solution is made；
The above-mentioned placebo solution of 30ml is taken, the right Ofloxacin standard items of 0.003125mmol are added thereto, sonic oscillation is molten
Solution, is settled to 50mL with above-mentioned blank control liquid, and the right Ofloxacin standard solution of 0.0625mmol/L is made；
2. lavo-ofloxacin and right Ofloxacin oxidation peak position determine
The chiral polypyrrole electrochemical sensor and Ag/AgCl reference electrode are inserted into 1mmol/L lavo-ofloxacin standard
In solution, saturated calomel electrode is inserted into saturated potassium chloride solution, in lavo-ofloxacin standard solution and saturated potassium chloride solution
Between build salt bridge, then connect the electrodes on electrochemical workstation, detected under room temperature using cyclic voltammetry, setting electricity
Bit scan range is -0.2~2.4V, and scanning speed 0.1V/s, circulating ring number is 1 circle, measures lavo-ofloxacin in 1.589V
There is an oxidation peak at place；Using above-mentioned same method, measure right Ofloxacin has an oxidation peak at 1.973V.
3. drawing standard curve and establishing equation of linear regression
The chiral polypyrrole electrochemical sensor and Ag/AgCl reference electrode are inserted into right Ofloxacin standard solution,
Saturated calomel electrode is inserted into saturated potassium chloride solution, builds salt between right Ofloxacin standard solution and saturated potassium chloride solution
Then bridge connects the electrodes on electrochemical workstation, detected under room temperature using cyclic voltammetry, and electric potential scanning model is arranged
It encloses for -0.2~2.4V, scanning speed 0.1V/s, circulating ring number is 1 circle, detects the above-mentioned right oxygen fluorine of five various concentrations respectively
Husky star standard solution obtains oxidation peak current numerical value of the right Ofloxacin standard solution of each concentration at 1.973V, according to peak current
The concentration of numerical value and standard solution draws right Ofloxacin concentration-current standard curve, and obtaining equation of linear regression is Y=
0.64611X+0.10683, and calculate coefficient R2=0.9998.
10. electrochemical detection method as claimed in claim 9, characterized in that in the step 2, precision weighs left oxygen fluorine
Husky star bulk pharmaceutical chemicals, are added the blank control liquid, and detection solution is prepared in sonic oscillation dissolution；
The chiral polypyrrole electrochemical sensor and Ag/AgCl reference electrode are inserted into the detection solution, calomel is saturated
Electrode is inserted into saturated potassium chloride solution, is built salt bridge between detection solution and saturated potassium chloride solution, is then connected electrode
It onto electrochemical workstation, is detected under room temperature using cyclic voltammetry, setting electric potential scanning range is -0.2~2.4V, is swept
Retouching speed is 0.1V/s, and circulating ring number is 1 circle, records the oxidation peak current numerical value at 1.973V, brings right Ofloxacin standard into
Curve linear regression equation Y=0.64611X+0.10683 calculates to obtain the concentration of right Ofloxacin in the detection liquid, converses a left side
The content of right Ofloxacin in Ofloxacin bulk pharmaceutical chemicals.
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