Determination of solvent residues in the hottest p

Determination of solvent residues in packaging materials

method standard for national drug packaging containers (materials) of the State Food and Drug Administration (Trial Implementation) YBB solvent residues in packaging materials China's new material industry in terms of variety, quality The test method for residue of solvent in packaging materials is applicable to the determination of residual solvents in pharmaceutical packaging materials. This method is based on gas-solid equilibrium. Take an area of sample and put it in a sealed container. Under certain humidity and time conditions, the residual organic solvent in the sample will volatilize by heating. After reaching equilibrium, take quantitative top air gas and inject it into the chromatograph for analysis to determine the retention time and peak area (or peak height). The results are expressed in mg/m2. For chromatographic conditions and system applicability test, the packed chromatographic column or capillary chromatographic column that can meet the separation requirements of the solvent to be tested can be selected. Packed chromatographic column: polyethylene glycol PEG-20M is generally used. Number of theoretical plates: not less than 1000. Unless otherwise specified, capillary chromatographic columns of similar polarity should be used interchangeably. Number of theoretical plates: no less than 5000. 1. Nonpolar chromatographic column: 100% dimethylpolysiloxane. 2. Polar chromatographic column: polyethylene glycol PEG-20M. 3. Medium polarity chromatographic column: 6% cyanopropyl phenyl-94% dimethylpolysiloxane. 4. Weak polarity chromatographic column: 5% phenyl-95% methyl polysiloxane. General selection: chromatographic column: 100% dimethylpolysiloxane 0.53mm 1.2m 30m detector: hydrogen flame ion detector determination conditions (for reference): column temperature 70 ℃, vaporization temperature 180 ℃, detection temperature 190 ℃. Split ratio: 5:1, nitrogen 5ml/min, hydrogen 40 ml/min, air 450 ml/min, resolution: more than 1.5, ethanol, isopropanol, ketone, ethyl acetate, toluene, butyl acetate, xylene can be separated. The preparation of the test article shall be sampled according to the proportion of internal surface area of 3~5cm2/ml, and the test article shall be prepared according to the provisions of the product, and placed in a glass container of appropriate volume, sealed. Preparation of reference substance 1. Take an appropriate amount of organic solvent to be tested with a micro sampler and inject it into a sealed glass container with an appropriate volume (the container contains 3 glass beads). Calculate the amount of organic solvent according to the density and volume of the organic solvent to be measured. 2. Accurately weigh an appropriate amount of organic solvent to be measured, dissolve it with appropriate solvent and dilute it to the appropriate concentration. Take an appropriate amount of the control solution and inject it into a sealed glass container with an appropriate volume (the container contains 3 glass beads). The selection of suitable solvent should not interfere with the determination of the solvent to be tested. In case of limit test, the volume or concentration of the reference substance shall be determined according to the limit of residual solvent. For quantitative determination, the volume or concentration of the reference substance shall be determined according to the actual residue of the solvent to be tested in the sample. Generally, the ratio of the chromatographic peak area of the reference substance to the chromatographic peak area of the corresponding residual solvent in the sample shall not exceed 2 times. If necessary, the volume or concentration of the reference substance should be adjusted according to the area of the sample. Determination method 1 external standard method unless otherwise specified, place the reference substance and sample in a 100 ℃ 2 ℃ incubator for 60 minutes (if necessary, place them in the range of 80~150 ℃ for 15 to 60 minutes according to the conditions of the material and the solvent to be tested, preferably higher than the boiling point of the solvent and lower than the decomposition temperature of the material). Shake them well before sampling, use a syringe preheated to the same temperature to extract 1ml of gas from the top of the container and inject it into the chromatograph. Record the chromatogram since 2009, measure the peak area (peak) of the reference substance and sample solvent to be tested, and calculate. The control sample is injected three times continuously, and the relative deviation of the results of the three times shall not exceed 10%. The second method is the standard curve method. Take five organic solvent reference substances with different concentrations to be tested (the linear range is determined according to the actual content of the organic solvent to be tested in the sample). Place it in a 100 ℃ 2 ℃ incubator for 60 minutes (if necessary, place it in the range of 80~150 ℃ for 15 to 60 minutes according to the conditions of the material and the solvent to be tested, and it is appropriate to be higher than the boiling point of the solvent and lower than the decomposition temperature of the material), use a syringe preheated to the same temperature to extract 1ml of gas from the top of the container and inject it into the gas chromatograph. Measure the peak area (or peak), and draw the standard curve between the peak area (peak) and the corresponding organic solvent quality. Take samples and place them in a 100 ℃ 2 ℃ incubator according to the standard curve method for 60 minutes. According to the peak area (peak) of the organic solvent to be measured in the sample, the mass of the solvent in the sample calculated from the standard curve is calculated according to the following formula. X=m/w, where: X --- residual amount of solvent in the sample, mg/m2; M --- mass of solvent to be tested, Mg; W --- surface area of sample,/m2. Drafting instructions for the determination method of solvent residues in packaging materials I. overview 1. Task source: this standard is formulated according to the relevant requirements of the notice on the preparation (Revision) of the 2004 drug packaging materials standard issued by the drug registration department of the State Food and Drug Administration (yjzh [2004] No. 26). 2. Objective: in order to further standardize the determination method of solvent residue in the product standard of pharmaceutical composite membrane and facilitate practical operation, this method is specially formulated. 3. Drafting principle: this standard project is established by referring to monitoring the levels of residual of residual solvents in flexible packaging materials (BS), flexible packaging materials Determination of residual solvents by static headspace gas chromatography (DIN en:), composite film for drug packaging, general rules for bags (YBB), and based on the format compiled in the appendix of Chinese Pharmacopoeia. The specific contents are based on the method name Principle, instrument and device, and determination method. 2、 Description of standard items 1. 3. Whether the sample is clamped correctly. The selection of sample taking area, glass bottle specification, heating temperature and time mainly refers to DIN EN:. The heating temperature in the gas-solid equilibrium directly affects the test results of the samples. The temperature selected is generally higher than the boiling point of the tested organic solvent, but some materials (such as LDPE) will decompose because the temperature is higher than its melting point, affecting the test results. Therefore, first of all, 100 is recommended as the heating temperature. 2. The pretreatment method of samples refers to the provisions of BS. Compared with the pretreatment method of samples in the general rules of pharmaceutical packaging composite film and bag (YBB), the direct placement method can avoid the impact of the size difference of cut samples on the results. 3. The choice of chromatographic column, as long as the measured organic solvent can be completely separated. 4. The purity of organic solvent standard solution shall not be less than 99.5%. 5. If the solvent content in the sample is not within the range of the standard curve, the range of the standard curve should be readjusted (NEO plastics can be diluted with a calibrated syringe to find a solution for sustainable packaging)