Chromatographic impurity, determination

Content, as well as impurity determinations, are done by chromatographic procedures such as gas chromatography (GC), high pressure liquid chromatography (HPLC) [831], capillary electrophoresis (CE) [832], and by spectroscopic techniques (UV, IR, MS, and NMR) [833, 834]. 

Inject 1 mL of a 0.1% (by volume) standard gas sample of each impurity in air into the chromatograph, and determine the absolute factor (Fa), in grams, per peak area (A) by the following formula ... 

British Pharmacepoeia (BP) and European Pharmacopoeia (EP) Applications of GC for the Assay Chromatographic Purity Identification Presence of Volatile Matter, Intermediates and Related Substances Organic Volatile Impurities Determination of Water Presence of Isomers and Racemate Ratios Determination of Alcohol and Miscellaneou s Uses of GC in Pharmaceutical Raw Materials and Dosage Forms. 

IPC method validation is similar to the drug substance and product method validation however, special consideration should be given to the sample reactivity and stability. IPC method validation requires coordination with the process chem-ist/engineers to provide fresh reaction and process samples for the analysis. Table 1 has a list of in-process validation parameters that should be evaluated for chromatographic IPC limit and quantitative tests. These parameters are based on the ICH guidelines.The IPC analyses are categorized into RAP (COR and impurity determination) and solution concentration assays (%, w/v % v/v and mg/mL). 

Injection repeatability Injection precision is measured by multiple injections, a minimiun of =6 is typically recommended, of the reference standard or sample solution at the 100% level and indicates the performance of the HPLC instrument using the chromatographic conditions on one particular day and in one laboratory. The relative standard deviation, RSD (%), as specified here, will determine the lowest variation limit of the analytical results. Repeatability for impurities determination is often assessed by making repeat injections typically = 6 of an impurity mixture and a statistical evaluation maybe performed using area response. 

Acrolein is produced according to the specifications in Table 3. Acetaldehyde and acetone are the principal carbonyl impurities in freshly distilled acrolein. Acrolein dimer accumulates at 0.50% in 30 days at 25°C. Analysis by two gas chromatographic methods with thermal conductivity detectors can determine all significant impurities in acrolein. The analysis with Porapak Q, 175—300 p.m (50—80 mesh), programmed from 60 to 250°C at 10°C/min, does not separate acetone, propionaldehyde, and propylene oxide from acrolein. These separations are made with 20% Tergitol E-35 on 250—350 p.m (45—60 mesh) Chromosorb W, kept at 40°C until acrolein elutes and then programmed rapidly to 190°C to elute the remaining components. 

Purity. Gas chromatographic analysis is performed utilizing a wide-bore capillary column (DB-1, 60 m x 0.32 mm ID x 1.0 //m film) and a flame ionization detector in an instmment such as a Hewlett-Packard 5890 gas chromatograph. A caUbration standard is used to determine response factors for all significant impurities, and external standard calculation techniques are used to estimate the impurity concentrations. AHyl chloride purity is deterrnined by difference. 

The distilled product was determined by the checkers to be 85-90% pure (gas chromatographic analysis), the major impurity being... 

The purity of the product is greater than 99% as determined by gas chromatographic analysis using a 6-m. column of 30% Carbowax 20M on 60-80 Chromosorb W. The major impurity (<1%) was shown to be 3-heptanol by comparison of gas chromatographic retention times and mass spectral fragmentation patterns with those of an authentic sample. 

Lipophilicity determination by CE exhibits the same advantages as all chromatographic methods, i.e. insensitivity to impurities, fast analysis time, low cost and... 

For the mixtures described under (3) it is sufficient to determine the chromatographic profile of the CRS and to demonstrate that all impurities are well separated according to the monograph description. When the spiked sample is also used in the purity control, then the content of the impurity in the CRS material must be determined by appropriate chromatographic methods and a value assigned to the material. 

Extraction or dissolution almost invariably will cause low-MW material in a polymer to be present to some extent in the solution to be chromatographed. Solvent peaks interfere especially in trace analysis solvent impurities also may interfere. For identification or determination of residual solvents in polymers it is mandatory to use solventless methods of analysis so as not to confuse solvents in which the sample is dissolved for analysis with residual solvents in the sample. Gas chromatographic methods for the analysis of some low-boiling substances in the manufacture of polyester polymers have been reviewed [129]. The contents of residual solvents (CH2C12, CgHsCI) and monomers (bisphenol A, dichlorodiphenyl sulfone) in commercial polycarbonates and polysulfones were determined. Also residual monomers in PVAc latices were analysed by GC methods [130]. GC was also... 

The purity of the solid solute also has fundamental analytical implications. In general, the analytical procedure employed for determining the solubility should be specific for the solute of interest. For this purpose, an analyte-specific chromatographic method (such as high-performance liquid chromatography, HPLC) is preferred. Such a method will also enable the impurities and any possible decomposition products to be identified and quantified. 

In moderately acidic solutions bromocriptine mesilate readily forms ion pairs with anionic dyes such as picric acid, bromothymol blue, methyl orange, which are extractable with an organic solvent. A procedure has been developed both for direct assay and for assay following chromatographic separation from the impurities. Therein bromocriptine mesilate is allowed to react with bromothymol blue at pH 2.5. The resulting ion pair is then extracted with benzene and its concentration determined at 410 nm (25). ... 

Various liquid chromatographic techniques have been frequently employed for the purification of commercial dyes for theoretical studies or for the exact determination of their toxicity and environmental pollution capacity. Thus, several sulphonated azo dyes were purified by using reversed-phase preparative HPLC. The chemical strctures, colour index names and numbers, and molecular masses of the sulphonated azo dyes included in the experiments are listed in Fig. 3.114. In order to determine the non-sulphonated azo dyes impurities, commercial dye samples were extracted with hexane, chloroform and ethyl acetate. Colourization of the organic phase indicated impurities. TLC carried out on silica and ODS stationary phases was also applied to control impurities. Mobile phases were composed of methanol, chloroform, acetone, ACN, 2-propanol, water and 0.1 M sodium sulphate depending on the type of stationary phase. Two ODS columns were employed for the analytical separation of dyes. The parameters of the columns were 150 X 3.9 mm i.d. particle size 4 /jm and 250 X 4.6 mm i.d. particle size 5 //m. Mobile phases consisted of methanol and 0.05 M aqueous ammonium acetate in various volume ratios. The flow rate was 0.9 ml/min and dyes were detected at 254 nm. Preparative separations were carried out in an ODS column (250 X 21.2 mm i.d.) using a flow rate of 13.5 ml/min. The composition of the mobile phases employed for the analytical and preparative separation of dyes is compiled in Table 3.33. 

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