Method for determining residual N, N-dimethylaminopropylamine in FPA98Cl anion exchange resin by using gas chromatography

Abstract

The invention relates to the technical field of gas chromatographic analysis, and discloses a method for determining N, N-dimethylaminopropylamine residues in FPA98Cl anion exchange resin by using gas chromatography, and the method comprises the following steps: S1, carrying out centrifugal separation on resin to obtain treated resin; s2, dissolving N, N-dimethylaminopropylamine in an organic solvent to obtain a reference substance solution; s3, diluting the reference substance solution into a reference substance solution with the concentration of 10%; s4, adding the treated resin into an organic solvent to obtain a test solution; s5, adding the treated resin into a reference solution with the concentration of 10% to obtain a standard test solution; and S6, setting parameters of a gas chromatograph, respectively and directly injecting the reference substance solution, the test solution and the standard test solution according to a certain sample injection amount, and calculating the residual quantity and the recovery rate of N, N-dimethylaminopropylamine according to a chromatogram. The method solves the problem that the residual quantity of N, N-dimethylaminopropylamine in resin cannot be quantitatively detected, and has the characteristics of better repeatability and higher sensitivity.

Description

Technical Field

[0001] The invention relates to the technical field of gas chromatography analysis, in particular to a method for determining residual N,N-dimethylaminopropylamine in FPA98 Cl anion exchange resin by utilizing gas chromatography. Background Art

[0002] Rohm and Haas FPA98 Cl anion exchange resin is a macroreticular anion exchange resin containing quaternary amine functional groups on a cross-linked polystyrene matrix. It has all the advantages of an acrylic matrix and a macroporous structure. This feature, combined with the strong alkaline ion exchange sites and the aromatic polymer backbone, makes it easy to adsorb high molecular weight organic matter. At the same time, as a macroporous resin, it is also called a fully porous resin and a polymer adsorbent. It is characterized by adsorption and has a high molecular weight polymer effect on concentrating and separating organic matter.

[0003] FPA98 Cl anion exchange resin mainly uses styrene and methyl acrylate as polymerization monomers, divinylbenzene as crosslinking agent, toluene, xylene, etc. as pore-forming agents, and plant cellulose substances as suspending agents, which are crosslinked and polymerized to form a porous skeleton structure of macroporous adsorption resin. Due to its good adsorption capacity, the monomer components are easy to polymerize, and it has the advantages of rapidity, convenience, sensitivity, and good selectivity, and is often used in the production process of pharmaceutical products.

[0004] In order to ensure the safety of pharmaceuticals during production and use and avoid the impact of resins on drug quality, the State Food and Drug Administration requires residual solvent inspection for products using macroporous resins. N,N-dimethylaminopropylamine is the main raw material for the production of FPA98 Cl anion exchange resin, and there may be certain residues in the resin. Therefore, the detection of N,N-dimethylaminopropylamine is of great significance for resin quality control.

[0005] However, the "Determination Method of Adsorption Resin Products for Food Industry" and patent literature do not record the detection of N,N-dimethylaminopropylamine in the resin; in the national standard QB / T 2851-2007, there is only a purity detection method for N,N-dimethylaminopropylamine, but this method has a high detection limit and cannot meet the quantitative detection of residual N,N-dimethylaminopropylamine in the resin. Summary of the invention

[0006] The object of the present invention is to provide a method for determining residual N,N-dimethylaminopropylamine in FPA98 Cl anion exchange resin by gas chromatography, so as to solve the problems raised in the above background technology.

[0007] To achieve the above object, the present invention provides the following technical solutions:

[0008] A method for determining residual N,N-dimethylaminopropylamine in FPA98 Cl anion exchange resin by gas chromatography comprises the following steps:

[0009] S1. Take 10 ml of resin and place it in a centrifuge tube. Centrifuge at 200 rpm for 5 min to remove free water on the surface to obtain the treated resin.

[0010] S2, weigh 10 mg of N, N-dimethylaminopropylamine, add 10 ml of organic solvent to dissolve, and obtain N, N-dimethylaminopropylamine solution; then weigh 0.9 ml of the N, N-dimethylaminopropylamine solution, add organic solvent to dilute to 100 ml, and obtain a reference substance solution;

[0011] S3, taking 10 ml of the reference solution obtained in step S2, adding an organic solvent to dilute to 100 ml, to obtain a reference solution with a concentration of 10%;

[0012] S4, weigh 2.5g of the treated resin obtained in step S1, add 25ml of organic solvent, treat with ultrasound in an ice bath for 20min, and let stand for 10min; take 20ml of the supernatant, concentrate and dry by rotary evaporation, add 2ml of organic solvent, and redissolve to obtain the test solution;

[0013] S5, weigh 2.5 g of the treated resin obtained in step S1, add 25 ml of a 10% reference solution, treat with ultrasound in an ice bath for 20 min, and let stand for 10 min; take 20 ml of the supernatant, concentrate and dry by rotary evaporation, add 2 ml of an organic solvent, and redissolve to obtain a spiked test solution;

[0014] S6. Set the parameters of the gas chromatograph, and under the parameters, directly inject the reference solution, the test solution and the spiked test solution at a certain injection volume, and record the chromatogram; based on the comparison of the chromatograms, determine whether there is any residual N,N-dimethylaminopropylamine in the test sample, and if so, calculate the residual amount and the recovery rate of N,N-dimethylaminopropylamine.

[0015] As a further solution of the present invention: in the steps S2 to S5, the organic solvent is one of anhydrous ethanol, anhydrous methanol and anhydrous acetonitrile.

[0016] As a further solution of the present invention: in the step S6, the parameters of the gas chromatograph are set as follows: the inlet temperature is 190-210°C, the carrier gas flow rate is 1.4-1.6 ml / min, the column temperature is 85-105°C, the detector temperature is 240-260°C, and the split ratio is (5-30):1.

[0017] As a further solution of the present invention: in the step S6, the parameters of the gas chromatograph are set as follows: the injection port temperature is 200°C, the carrier gas flow rate is 1.5 ml / min, the column temperature is 90°C, the detector temperature is 250°C, and the split ratio is 5:1.

[0018] As a further solution of the present invention: in the step S6, the injection volume of the reference solution, the test solution and the spiked test solution is 1.0 to 3.0 μl.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] The invention comprises the following steps: dissolving and diluting N,N-dimethylaminopropylamine in an organic solvent to obtain a reference solution; preparing reference solutions of different concentrations; preparing a test solution by mixing the treated resin with the organic solvent; preparing a spiked test solution; setting different parameters on a gas chromatograph, injecting the reference solution, the test solution and the spiked test solution respectively, and calculating the residual amount and the recovery rate of N,N-dimethylaminopropylamine according to the comparison of the chromatograms. The method solves the problem that the residual amount of N,N-dimethylaminopropylamine in the resin cannot be quantitatively detected, and has the characteristics of good repeatability and high sensitivity. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 is a chromatogram of the baseline noise of the blank solution of the present invention;

[0022] Figure 2 is the chromatogram of the blank solution of the present invention;

[0023] Figure 3 is the chromatogram of the quantitative limit solution of the present invention;

[0024] Figure 4 is the chromatogram of the detection limit solution of the present invention;

[0025] Figure 5 is a chromatogram of the reference substance solution of the present invention;

[0026] Figure 6 It is a chromatogram of the test solution of the present invention;

[0027] Figure 7 The chromatogram of the spiked test solution of the present invention;

[0028] Figure 8 It is the chromatogram of the accuracy solution of the present invention. DETAILED DESCRIPTION

[0029] Example 1

[0030] In an embodiment of the present invention, a method for determining residual N,N-dimethylaminopropylamine in FPA98 Cl anion exchange resin by gas chromatography comprises the following steps:

[0031] S1. Take 10 ml of resin and place it in a centrifuge tube. Centrifuge at 200 rpm for 5 min to remove free water on the surface to obtain the treated resin.

[0032] S2. Weigh 10 mg of N,N-dimethylaminopropylamine, add 10 ml of anhydrous ethanol to dissolve, and obtain an N,N-dimethylaminopropylamine solution; then weigh 0.9 ml of the N,N-dimethylaminopropylamine solution, add anhydrous ethanol to dilute to 100 ml, and obtain a reference substance solution;

[0033] S3, measure 10 ml of the reference solution obtained in step S2, add anhydrous ethanol to dilute to 100 ml, and obtain a reference solution with a concentration of 10%;

[0034] S4, weigh 2.5 g of the treated resin obtained in step S1, add 25 ml of anhydrous ethanol, treat with ultrasound in an ice bath for 20 min, and let stand for 10 min; take 20 ml of the supernatant, concentrate and dry by rotary evaporation, add 2 ml of anhydrous ethanol, and redissolve to obtain the test solution;

[0035] S5, weigh 2.5g of the treated resin obtained in step S1, add 25ml of a 10% reference solution, treat with ultrasound in an ice bath for 20min, and let stand for 10min; take 20ml of the supernatant, concentrate and dry by rotary evaporation, add 2ml of anhydrous ethanol, and redissolve to obtain a spiked test solution;

[0036] S6. Set the parameters of the gas chromatograph as follows: the injection port temperature is 190°C, the carrier gas flow rate is 1.4 ml / min, the column temperature is 90°C, the detector temperature is 250°C, and the split ratio is 5:1. Under these parameters, directly inject the reference solution, the test solution and the spiked test solution with an injection volume of 1.0 μl, and record the chromatogram. Based on the comparison of the chromatograms, determine whether there is any residual N,N-dimethylaminopropylamine in the test sample. If so, calculate the residual amount and the recovery rate of N,N-dimethylaminopropylamine.

[0037] Example 2

[0038] In an embodiment of the present invention, a method for determining residual N,N-dimethylaminopropylamine in FPA98 Cl anion exchange resin by gas chromatography comprises the following steps:

[0039] S1. Take 10 ml of resin and place it in a centrifuge tube. Centrifuge at 200 rpm for 5 min to remove free water on the surface to obtain the treated resin.

[0040] S2. Weigh 10 mg of N,N-dimethylaminopropylamine, add 10 ml of anhydrous ethanol to dissolve, and obtain an N,N-dimethylaminopropylamine solution; then weigh 0.9 ml of the above solution, add anhydrous ethanol to dilute to 100 ml, and obtain a reference solution;

[0041] S3, measure 10 ml of the reference solution obtained in step S2, add anhydrous ethanol to dilute to 100 ml, and obtain a reference solution with a concentration of 10%;

[0042] S4, weigh 2.5 g of the treated resin obtained in step S1, add 25 ml of anhydrous ethanol, treat with ultrasound in an ice bath for 20 min, and let stand for 10 min; take 20 ml of the supernatant, concentrate and dry by rotary evaporation, add 2 ml of anhydrous ethanol, and redissolve to obtain the test solution;

[0043] S5, weigh 2.5g of the treated resin obtained in step S1, add 25ml of a 10% reference solution, treat with ultrasound in an ice bath for 20min, and let stand for 10min; take 20ml of the supernatant, concentrate and dry by rotary evaporation, add 2ml of anhydrous ethanol, and redissolve to obtain a spiked test solution;

[0044] S6. Set the parameters of the gas chromatograph as follows: the injection port temperature is 200°C, the carrier gas flow rate is 1.5 ml / min, the column temperature is 90°C, the detector temperature is 250°C, and the split ratio is 5:1. Under these parameters, directly inject the reference solution, the test solution and the spiked test solution with an injection volume of 2 μl, and record the chromatogram. Based on the comparison of the chromatograms, determine whether there is any residual N,N-dimethylaminopropylamine in the test sample. If so, calculate the residual amount and the recovery rate of N,N-dimethylaminopropylamine.

[0045] Example 3

[0046] In an embodiment of the present invention, a method for determining residual N,N-dimethylaminopropylamine in FPA98 Cl anion exchange resin by gas chromatography comprises the following steps:

[0047] S1. Take 10 ml of resin and place it in a centrifuge tube. Centrifuge at 200 rpm for 5 min to remove free water on the surface to obtain the treated resin.

[0048] S2. Weigh 10 mg of N,N-dimethylaminopropylamine, add 10 ml of anhydrous ethanol to dissolve, and obtain an N,N-dimethylaminopropylamine solution; then weigh 0.9 ml of the above solution, add anhydrous ethanol to dilute to 100 ml, and obtain a reference solution;

[0049] S3, measure 10 ml of the reference solution obtained in step S2, add anhydrous ethanol to dilute to 100 ml, and obtain a reference solution with a concentration of 10%;

[0050] S4, weigh 2.5 g of the treated resin obtained in step S1, add 25 ml of anhydrous ethanol, treat with ultrasound in an ice bath for 20 min, and let stand for 10 min; take 20 ml of the supernatant, concentrate and dry by rotary evaporation, add 2 ml of anhydrous ethanol, and redissolve to obtain the test solution;

[0051] S5, weigh 2.5g of the treated resin obtained in step S1, add 25ml of a 10% reference solution, treat with ultrasound in an ice bath for 20min, and let stand for 10min; take 20ml of the supernatant, concentrate and dry by rotary evaporation, add 2ml of anhydrous ethanol, and redissolve to obtain a spiked test solution;

[0052] S6. Set the parameters of the gas chromatograph as follows: the injection port temperature is 200°C, the carrier gas flow rate is 1.5 ml / min, the column temperature is 90°C, the detector temperature is 250°C, and the split ratio is 20:1. Under these parameters, directly inject the reference solution, the test solution and the spiked test solution with an injection volume of 3.0 μl, and record the chromatogram. Based on the comparison of the chromatograms, determine whether there is any residual N,N-dimethylaminopropylamine in the test sample. If so, calculate the residual amount and the recovery rate of N,N-dimethylaminopropylamine.

[0053] 1. Calculation of detection limit and quantification limit:

[0054] Take appropriate amount of the reference solution obtained in Example 2, dilute it with anhydrous ethanol to a concentration of 1.0 μg / ml, which is defined as the quantitative limit solution; dilute it with anhydrous ethanol to a concentration of 0.4 μg / ml, which is defined as the detection limit solution; define anhydrous ethanol as the blank solution;

[0055] According to the gas chromatography parameters in Example 2, the reference solution, the test solution and the spiked test solution were directly injected with an injection volume of 2.0 μl, wherein the quantitative limit solution was injected 6 times continuously, and the chromatogram was recorded.

[0056] Based on the comparison of the chromatograms, the detection limit and quantification limit of N,N-dimethylaminopropylamine were calculated. The results are shown in Tables 1 to 3.

[0057] Table 1 Baseline noise monitoring results in blank solution

[0058] Solution name Baseline noise (AU / h) Blank solution 1 0.216 Blank solution 2 0.216 Blank solution 3 0.221 average value 0.218

[0059] Table 2 Detection limit results

[0060] Detection limit solution concentration Peak area pA*s S / N 0.4μg / ml 0.436 3.8

[0061] Table 3 Quantitation limit results

[0062]

[0063]

[0064] According to the results in Tables 1 to 3, the detection limit of N,N-dimethylaminopropylamine in the method adopted by the present invention is 0.4 μg / ml; the quantification limit is 1.0 μg / ml, and the RSD of the peak area of ​​repeated injections is 0.2%, the repetition is good, and the detection sensitivity of the method is high.

[0065] 2. Repeatability calculation:

[0066] The chromatograms obtained in Example 2 were compared to determine whether the test sample contained N,N-dimethylaminopropylamine residues, and the residual amount and the recovery rate of N,N-dimethylaminopropylamine were calculated. The results are shown in Table 4.

[0067] Table 4 Accuracy recovery results

[0068]

[0069] According to Table 4, the method used in the present invention has good precision and high recovery rate.

[0070] 3. Durability Test

[0071] The recovery rate of N,N-dimethylaminopropylamine in Examples 1 to 3 was calculated under different chromatographic conditions of injection port temperature, column temperature, carrier gas flow rate and detector temperature to investigate its durability. The results are shown in Table 5.

[0072] Table 5 Durability results

[0073]

[0074] According to Table 5, in the method adopted by the present invention, under the conditions of the injection port temperature of 190-210°C, the column temperature of 85-105°C, the carrier gas flow rate of 1.4-1.6 ml / min, and the detector temperature of 240-260°C, the method has good durability and the recovery rate of N,N-dimethylaminopropylamine is between 95% and 105%.

[0075] What is described above is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

Claims

1. A method for determining residual N,N-dimethylaminopropylamine in FPA98 Cl anion exchange resin by gas chromatography, characterized in that: The following steps are involved: S1. Take 10 ml of resin and place it in a centrifuge tube. Centrifuge at 200 rpm for 5 min to remove free water on the surface to obtain the treated resin. S2, weigh 10 mg of N, N-dimethylaminopropylamine, add 10 ml of organic solvent to dissolve, and obtain N, N-dimethylaminopropylamine solution; then weigh 0.9 ml of the N, N-dimethylaminopropylamine solution, add organic solvent to dilute to 100 ml, and obtain a reference substance solution; S3, taking 10 ml of the reference solution obtained in step S2, adding an organic solvent to dilute to 100 ml, to obtain a reference solution with a concentration of 10%; S4, weigh 2.5g of the treated resin obtained in step S1, add 25ml of organic solvent, treat with ultrasound in an ice bath for 20min, and let stand for 10min; take 20ml of the supernatant, concentrate and dry by rotary evaporation, add 2ml of organic solvent, and redissolve to obtain the test solution; S5, weigh 2.5 g of the treated resin obtained in step S1, add 25 ml of a 10% reference solution, treat with ultrasound in an ice bath for 20 min, and let stand for 10 min; take 20 ml of the supernatant, concentrate and dry by rotary evaporation, add 2 ml of an organic solvent, and redissolve to obtain a spiked test solution; S6. Set the parameters of the gas chromatograph, and under the parameters, directly inject the reference solution, the test solution and the spiked test solution at a certain injection volume, and record the chromatogram; based on the comparison of the chromatograms, determine whether there is any residual N,N-dimethylaminopropylamine in the test sample, and if so, calculate the residual amount and the recovery rate of N,N-dimethylaminopropylamine.

2. The method for determining residual N,N-dimethylaminopropylamine in FPA98 Cl anion exchange resin by gas chromatography according to claim 1, characterized in that: In the steps S2 to S5, the organic solvent is one of anhydrous ethanol, anhydrous methanol and anhydrous acetonitrile.

3. The method for determining residual N,N-dimethylaminopropylamine in FPA98 Cl anion exchange resin by gas chromatography according to claim 1, characterized in that: In the step S6, the parameters of the gas chromatograph are set as follows: the injection port temperature is 190-210°C, the carrier gas flow rate is 1.4-1.6 ml / min, the column temperature is 85-105°C, the detector temperature is 240-260°C, and the split ratio is (5-30):

1.

4. The method for determining residual N,N-dimethylaminopropylamine in FPA98 Cl anion exchange resin by gas chromatography according to claim 1, characterized in that: In the step S6, the parameters of the gas chromatograph are set as follows: the injection port temperature is 200°C, the carrier gas flow rate is 1.5 ml / min, the column temperature is 90°C, the detector temperature is 250°C, and the split ratio is 5:

1.

5. The method for determining residual N,N-dimethylaminopropylamine in FPA98 Cl anion exchange resin by gas chromatography according to claim 1, characterized in that: In the step S6, the injection volume of the reference solution, the test solution and the spiked test solution is 1.0 to 3.0 μl.

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