Specific Identification Tests

Guidance on specifications is divided into universal tests/criteria which are considered generally applicable to all new substances/products and specific tests/criteria which may need to be addressed on a case-by-case basis when they have an impact on the quality for batch control. Tests are expected to follow the ICH guideline on analytical validation (Section 13.5.4). Identification of the drug substance is included in the universal category, and such a test must be able discriminate between compounds of closely related structure which are likely to be present. It is acknowledged here that optically active substances may need specific identification testing or performance of a chiral assay in addition to this requirement. 

Four distinct classes of Caramel can be distinguished by the reactants used in their manufacture and by specific identification tests ... 

A specific identification test for urea is the enzymatic reaction with urease. 50 mg of powdered resin or 0.1 ml of the resin solution is carefully heated in a test tube with a Bunsen burner until all formaldehyde has been removed (check odor ). After cooling and neutralizing with 10% sodium hydroxide using phenolphthalein as an indicator, 1 drop of 1 N sulfuric acid and 0.2 ml of a freshly prepared 10% urease solution are added. A moist piece of litmus paper is then attached to the upper rim of the test tube. After a short time, the blue coloration of the indicator paper demonstrates the presence of ammonia which is formed only by urea-containing resins and not by melamine resins. Hexamethylene tetramine is the only substance that may interfere with this reaction. 

Characteristic elements (N, Cl, F, S, Si), individual identification tests (Compare Chapter 4 "Testing for Heteroatoms and Chapter 6 "Specific Identification Tests )... 

Testing of phthalocyanines includes crystallization (qv), flocculation, and appHcation in paints, plastics (qv), and printing inks (1). The ASTM standard specifications include CuPc in dry powder form for various appHcations (153). The specifications cover color (qv), character or tint, oil absorption, reactions in identification tests, and dispersions and storage stabiUty. Quantitative deterrninations are possible with ceric sulfate (30) or sodium vanadate (154). Identification methods are given (155), including tests for different appHcations. 

An enzymatic method (45), which is specific for the citrate moiety, can be used as a combined assay and identification test for citric acid and its common salts down to 20 ppm. 

Where antioxidants or antimicrobial preservatives are used, the finished product release specification will need to include identification tests and assays for these two types of excipient. The shelf life specification should also include a specification for assay for antimicrobial preservatives. Stability data will be required for both antioxidants and antimicrobial preservatives in the finished product, and in addition the preservative efficacy of the formulated product should be examined over its shelf life and by means of appropriate in-use stability tests. Preservative efficacy data should also be presented at the lower limit of the preservative assay. 

Si element ATR-FTIR spectroscopy was used to analyze this residue, and its spectrum, along with the closest library matches, are shown in Figure 41. The absorbance of this residue is low as a consequence of the thin layer present on the plate. This makes matching the sample spectrum with a reference spectrum somewhat difficult. The closest matches extracted from the library interrogated are to ester-based plasticizer materials, which is consistent with a phthalate-plasticized PVC. A more specific identification could have been made with further testing such as subjecting the residue to GC-MS analysis, but the information suggested by the ATR-FTIR analysis was, in this case sufficient. 

Part—I has three chapters that exclusively deal with General Aspects of pharmaceutical analysis. Chapter 1 focuses on the pharmaceutical chemicals and their respective purity and management. Critical information with regard to description of the finished product, sampling procedures, bioavailability, identification tests, physical constants and miscellaneous characteristics, such as ash values, loss on drying, clarity and color of solution, specific tests, limit tests of metallic and non-metallic impurities, limits of moisture content, volatile and non-volatile matter and lastly residue on ignition have also been dealt with. Each section provides adequate procedural details supported by ample typical examples from the Official Compendia. Chapter 2 embraces the theory and technique of quantitative analysis with specific emphasis on volumetric analysis, volumetric apparatus, their specifications, standardization and utility. It also includes biomedical analytical chemistry, colorimetric assays, theory and assay of biochemicals, such as urea, bilirubin, cholesterol and enzymatic assays, such as alkaline phosphatase, lactate dehydrogenase, salient features of radioimmunoassay and automated methods of chemical analysis. Chapter 3 provides special emphasis on errors in pharmaceutical analysis and their statistical validation. The first aspect is related to errors in pharmaceutical analysis and embodies classification of errors, accuracy, precision and makes... 

The data from the density (specific gravity) test method (ASTM D1298 IP 160) provides a means of identification of a grade of naphtha but is not a guarantee of composition and can only be used to indicate evaluate product composition or quality when used in conjunction with the data from other test methods. Density data are used primarily to convert naphtha volume to a weight basis, a requirement in many of the industries concerned. For the necessary temperature corrections and also for volume corrections, the appropriate sections of the petroleum measurement tables (ASTM D1250 IP 200) are used. 

Identification (ID) tests in Category IV require only specificity for their validation. Identification by HPLC usually involves comparison of the retention time (%) or relative retention time (RRT) of a sample and standard injection. The increasing use of photodiode array (PDA) detectors in HPLC methods also allows identification by comparison of UV spectra for standards and samples, in addition to retention characteristics. The information required for either ID test by HPLC can be gathered while performing any other HPLC method for a given sample. Identification tests are often incorporated into the assay method and the satisfactory completion of specificity for the assay will meet the requirements for ID as well. 

There is no single expression form for specificity. It is rather something which must be demonstrated. The way in which this is done depends on the objective and the type of analytical method (see also below). For identification tests, the goal is to ensure the identity of an analyte. Specificity is here the abihty to discriminate between compounds of closely related structures which can be present. 

Excipients used in injectable formulations have to meet several stringent requirements. A positive identification test uniquely applicable to the excipients is required (e.g., infrared spectrophotometry and chromatography). It is important that manufacturers identify and set appropriate limits for impurities. These limits should be based upon appropriate toxicological data, or the limits described in national compendial requirements. Manufacturing processes should be adequately controlled so that the impurities do not exceed such established specifications. Solvents or catalysts used in the excipient production process should be removed to appropriate levels. If naturally derived, excipients should meet endotoxin levels and may require further testing for bovine spongiform encephalopathy (BSE) /... 

The absolute method relies on the UV spectrophotometer being accurate in the measurement of wavelength and intensity, and the B.P. specifies methods for the calibration of both. However, UV-Vis spectra are not specific for any one particular substance, as many UV absorbing molecules have similar UV spectra, and this method is used in conjunction with several identification tests, as described in the B.P. 

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