Gas chromatograph for residual solvents in pharmaceutical packaging materials
1、 Product Description

YBB00312004-2015 Packaging Material Solvent Residual Determination Method

This method is applicable to the determination of residual solvents in pharmaceutical packaging materials. The residual solvents in drug packaging materials refer to organic volatile compounds used in the raw and auxiliary materials of drug packaging materials and production processes, but not completely removed during the production process of drug packaging materials. The residual amount of organic solvents in drug packaging materials should comply with the regulations under each variety. The types of solvents that need to be tested should be determined based on the characteristics of the product formula and process, not limited to the solvents listed in this standard. This method is based on gas cycle equilibrium. A certain area of the sample is placed in a sealed container. Under certain temperature and time conditions, the residual organic solvent in the sample evaporates when heated. After reaching equilibrium, the headspace gas is quantitatively injected into the chromatograph for qualitative retention time and quantitative peak area analysis. The limit of residual solvents determined by the residual solvent determination method (General Rule 0861 of the 2015 edition of the Chinese Pharmacopoeia) should meet the requirements of each variety item. The detection limit of each solvent for benzene and its derivatives should not be higher than 0.01mg/m, and it should change with the increase of sensitivity of the inspection method.

Chromatographic conditions and system suitability test

The chromatographic column can be selected as a capillary column or other suitable chromatographic column that can meet the separation requirements of the solvent to be tested. The chromatographic peak of the substance to be tested should be calculated, and the theoretical plate number of the packed column should generally not be less than 1000.

Unless otherwise specified, capillary chromatography columns of similar polarity can be used interchangeably. Theoretical board count: not less than 5000.

1. Non polar color column: 100% polydimethylsiloxane fired.

2. Polar chromatography column: Polyethylene glycol PEG-20M.

3. Medium polarity chromatography column: 6% cyanoalkylphenyl-94% dimethylsilane.

4. Feather polarity chromatography column: 5% phenyl-95% methyl polysiloxane.

-General selection:

Chromatographic column (60mX0.32mmx0.5ym)

Detector: Flame Ionization Detector (FID)

Measurement conditions (for reference): Column temperature: Initial temperature of 50 ℃, hold for 5 minutes, then increase at a rate of 10 ℃ per minute

Temperature up to 150 ℃, injection temperature at 200 ℃, detector temperature at 220 ℃,

Split ratio: 10:1

Nitrogen 2ml/min, hydrogen 40ml/min, air 400ml/min

Separation degree: The separation degree between the chromatographic peak of the test substance and its adjacent peaks should be greater than 1.5.

The relative standard deviation of the peak area of the analyte should not exceed 10%.

Separable methanol, isoamyl alcohol, ketone, butanone, ethyl acetate, butyl acetate, benzene, toluene, ethylbenzene, para xylene

O-xylene, m-xylene, etc.

Preparation of test samples

2、 Instrument configuration
Product Name, Model, Specification, and Description
Gas chromatograph GC2090 FID, capillary gasification chamber injection system
Chromatography workstation dual channel (computer, printer self equipped)
30 meter capillary column for chromatography
Headspace sampler contains 100 headspace bottles
High purity hydrogen generator HK-3 hydrogen flow rate 300ml/min
High purity air generator AK-2 air flow rate 2000ml/min
High purity nitrogen cylinder 40L nitrogen flow rate 300ml/min
Test reagents
Four types of benzene and its derivatives (benzene, toluene, ethylbenzene, xylene):
4 types of alcohols (methanol, ethanol, isopropanol, n-butanol)
Four types of ketones (acetone, 4-methyl-2-pentanone, butanone, cyclohexanone);
4 esters (ethyl acetate, n-propyl acetate, n-butyl acetate, isopropyl acetate);
One type of ether (propylene glycol methyl ether) and solvent matrix (triacetin glycerol ester).

3、 Preparation of standard solution
Accurately weigh 20-30 mg each of benzene and its derivatives, and approximately 350-450 mg each of alcohols, esters, and ethers in a 250 mL volumetric flask. Dilute with glycerol triacetate to obtain the first level standard solution. On this basis, other standard solutions are gradually diluted with glycerol triacetate at a 5-fold ratio, resulting in a total of 5 levels of mixed standard solutions. These solutions are stored in the refrigerator for future use and should be placed at room temperature before sampling.
4、 Sample processing
Take an appropriate amount of ink and use a colorimeter or other tool to apply it onto copperplate paper or white cardboard to prepare a sample. The thickness of the sample should be controlled at (35+5) μ m. After preparation, suspend the sample and let it stand for 2 hours. Environmental conditions: temperature (25 ± 1) ℃, relative humidity (65 ± 5)%. According to the standard conditions and requirements, cut the sample into 22.0 cm x 5.5cm (equivalent to 121cm2=0.0121m), cut the copperplate paper into 15.5cm~10cm (equivalent to 155cm2=0.0155), roll the printing side inward into a simple package, quickly place it in the headspace injection bottle, add 1mL of triacetin glycerol ester and tightly seal the bottle cap.
4、 Instrument operating conditions
Column temperature: Initial temperature of 50 ℃, equilibrium time of 13 minutes; Heating rate 5 ℃/min, termination temperature 180 ℃, equilibrium time 25 minutes
Vaporization temperature: 260℃
Detector temperature: 260 ℃
Carrier gas pressure: 0.1Mpa; Split flow: 30ml/min; Tail blowing: 30ml/min; Diaphragm cleaning: 3ml/min;