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The organic solvent residue gas chromatograph method drugs

Source:未知 Posted:2015-08-12 23:53 Browse:

Drug residual solvent means the drug substance or excipients of production, as well as for use in the preparation of formulations, but in the process failed to completely remove the organic solvent. According to product specifications, pharmaceutical production and quality management practices, combined with the characteristics of the production process, develop the appropriate limits of common medicines residual solvent. Gas chromatography detection of residual solvents in pharmaceutical method steps as follows.
 
First, the GC column selection
 1. GC analysis using capillary column selection, unless otherwise specified, can be used interchangeably between similar polarity similar column.
    (1) non-polar column: stationary phase is 100% dimethylpolysiloxane capillary column;
    (2) polar column: stationary phase is polyethylene glycol (PEG-20M) capillary column;
    (3) polar column: stationary phase of (35%) diphenyl - 65%) Polyoxyethylene methyl silane, 50%) diphenyl - (50%) polyethylene oxide dimethyl silane, (35% ) diphenyl - 65%), polyethylene oxide dimethyl silane, 14%) cyanopropyl phenyl - (86%) dimethylpolysiloxane, (6%) cyanopropyl phenyl - (86%) dimethylpolysiloxane capillary column and the like;
    (4) less polar column: stationary phase of (5%) phenyl - (95%) Polyoxyethylene methyl silane, (5%) diphenyl - (95%) dimethylsiloxane copolymer Capillary Column and so on.
 
 2. Packed Column
   With a diameter of 0.25-0.18mm divinylbenzene - ethyl vinyl benzene type porous polymer beads or other suitable filler as the stationary phase.
 
 3. Column suitability test
  (1) calculated using the analyte peak, the number of theoretical plates capillary columns generally not less than 5,000; theoretical plate packed column method is generally not less than 1000;
  (2) chromatogram peak separation analyte peak adjacent thereto should be greater than 1.5;
  (3) within a standard method for quantitative analysis, control solution sample 5 consecutive times, resulting analyte and the relative standard deviation ratio of the internal standard peak area (RSD) should not exceed 5%; if outside the standard method, The resulting analyte peak area RSD should not exceed 10%.
 
Two prepared test sample solution
 1, headspace
    Unless otherwise specified, the test accurately weighed 0.1 ~ 1g; usually with water as solvent; for non-water-soluble drugs, can be N, N- dimethyl formamide, dimethyl sulfoxide, or other suitable solvent; According to the solubility of the test and the test solvent, select a suitable solvent and should not interfere with the determination of the test solvent. Test solution according to the prescribed limits under variety of preparation for the entry of residual solvent, its concentration should meet the needs of the system of quantitative determination.
 2. Direct injection solution
    Precision Weigh the test amount, water or an appropriate organic solvent to dissolve; the provisions of preparation of the test solution in accordance with the limits under variety of items residual solvent, the concentration should meet the needs of the system of quantitative determination.
 Preparation of the reference solution 3,
    Precision said predetermined items of all varieties to take the right amount of organic solvent checking, and sample solution was prepared using the same preparation of the reference solution for solvent; such as water as a solvent, an organic solvent should be tested first dissolved in 50% dimethyl sulfoxide or N, N- dimethylformamide solution, and then gradually diluted with water. If the limit test, determining the concentration of the reference solution in accordance with the prescribed limits of residual solvent; if the quantitative determination, in order to ensure the accuracy of the quantitative results, should determine the concentration of the reference solution based on the actual residues of the test residual solvent; peak area is usually the peak area of ​​the test solution and reference solution corresponding residual solvent is preferably not more than 2 times. If necessary, re-adjust the concentration of the test solution or the reference solution.
 
Third, the measurement method
 1. Capillary Column air injection isothermal
    When the amount of organic solvent to be checked much, and less polar differences, we can use this method.
    Chromatographic conditions: column temperature is generally 40 ~ 100 ℃; often with nitrogen as a carrier gas flow rate of 1.0 ~ 2.0ml per minute; when using water as solvent vial equilibrium temperature of 70 ~ 85 ℃ vial equilibration time of 30 ~ 60 minutes; inlet temperature of 200 ℃; such as using a flame ionization detector (FID), a temperature of 250 ℃.
Determination: reference solution and the test solution, respectively successive injections less than 2 times, the differential measurement measured peak area of ​​the chromatogram unknown organic solvent.
 
 2. Capillary Column air inlet system programmed temperature method
    When you need to check a larger number of organic solvents organic solvents, and the polarity difference is large, this method can be used.
    Chromatographic conditions: Column generally maintained at 40 ℃ 8 first minutes, then 8 ℃ / min ramped 120 ℃, for 10 minutes; the top when using water as a solvent; with nitrogen as a carrier gas flow rate of 2.0ml per minute Empty temperature equilibrium temperature of 70 ~ 85 ℃ vial equilibration time of 30 to 60 minutes; inlet temperature of 200 ℃; such as using FID detector temperature of 250 ℃.
    Determination: reference solution and the test solution, respectively successive injections less than 2 times, measured peak area measured. Chromatogram identification of unknown organic solvent.
 
 3. Direct Inject solution
    May be packed columns, we can use a suitable polar capillary column Determination of the reference solution and the test solution, respectively, consecutive injections 2-3 times, measured peak area measured.
 
Fourth, the calculation method
  (1) Limit Test: Unless otherwise specified, according to the concentration of the test solution was measured under subparagraph varieties. Standard method when measured ratio of the area of ​​the internal standard peak area obtained for the sample solution measured the ratio of the solvent peak is not greater than the corresponding reference solution. When measured outside the standard method, and the resulting solution was measured for the sample solvent peak area no larger than the corresponding area of ​​the reference solution peak.
  (2) Quantitative determination: Analysis of the various residual solvents according to the internal standard method or external standard.