Identity testing

Hydantoin itself can be detected ia small concentrations ia the presence of other NH-containing compounds by paper chromatography followed by detection with a mercury acetate—diphenylcarba2one spray reagent. A variety of analytical reactions has been developed for 5,5-disubstituted hydantoias, due to their medicinal iaterest. These reactions are best exemplified by reference to the assays used for 5,5-diphenylhydantoiQ (73—78), most of which are based on their cycHc ureide stmcture. Identity tests iaclude the foUowiag (/) the Zwikker reaction, consisting of the formation of a colored complex on treatment with cobalt(II) salts ia the presence of an amine (2) formation of colored copper complexes and (3) precipitation on addition of silver(I) species, due to formation of iasoluble salts at N. ... 

There are several comprehensive reviews of analytical methods for vitamin K (19,20). Owiag to the preseace of a aaphthoquiaoae aucleus, the majority of analytical methods use this stmctural feature as a basis for analysis. Several identity tests such as its reaction with sodium bisulfite or its uv spectmm exploit this characteristic. Although not specific, titrimetric, polarographic, and potentiometric methods have also been used (20). 

For drug substances and drug products, applications for enantiomers and racemates should include a stereochemically specific identity test and/or a stereochemically selective assay. The choice of control tests should be based on the method of manufacture and stability characteristics and, in the case of the finished product, its composition. 

Creep modeling A stress-strain diagram is a significant source of data for a material. In metals, for example, most of the needed data for mechanical property considerations are obtained from a stress-strain diagram. In plastic, however, the viscoelasticity causes an initial deformation at a specific load and temperature and is followed by a continuous increase in strain under identical test conditions until the product is either dimensionally out of tolerance or fails in rupture as a result of excessive deformation. This type of an occurrence can be explained with the aid of the Maxwell model shown in Fig. 2-24. 

One approach, and the first to be adopted, is to study transmitter release from slices which have been preloaded with radiolabelled transmitter. In these experiments, drug-induced changes in the release of transmitter is usually monitored using the doublepulse technique. This involves comparing the effects of a test drug on the amount of transmitter released in response to a reference pulse and a second identical test pulse. If all the radiolabelled transmitter that overflows in the effluent is collected, and the amount which remains in the slice at the end of the experiment is also measured, it is possible to calculate not only how much radiolabelled transmitter was originally contained in the slice but also the effects of drugs on fractional release , i.e. the proportion of the store of radiolabelled transmitter which is released by nerve stimulation. As with... 

At least one test shall be conducted to verify the identity of each component of a drug product. Specific identity tests, if they exist, shall be used. 

Each component shall be tested for conformity with all appropriate written specifications for purity, strength, and quality. In lieu of such testing by the manufacturer, a report of analysis may be accepted from the supplier of a component, provided that at least one specific identity test is conducted on such component by the manufacturer, and provided that the manufacturer establishes the reliability of the... 

Repeatability is defined as precision under conditions where independent test results are obtained with the same method on identical test material in the same laboratory by the same operator using the same equipment within short intervals of time. The replicate analytical portion for testing can be prepared from a common field sample containing incurred residues. This approach is used extremely rarely. Normally, repeatability is estimated by the relative standard deviation ofrecoveries, which should be lower than 20% per commodity and fortification levels according to SANCO/825/00. In justified cases, higher variability can be accepted. 

Table 41.3 shows a performance comparison of Pt/Pd TUD-1 with a commercial Pt/Pd catalyst (26). The feedstock is a typical straight run gasoil ( SRGO ), a distillate precursor to diesel fuel. Under identical test conditions, the TUD-1 catalyst achieved 75% aromatics saturation versus 50% for the same volume of commercial catalyst. This superior result is particularly interesting because the TUD-1 catalyst had a much lower density than the commercial material, so that less catalyst by weight was required in the reactor. 

The closeness of agreement between independent results obtained with the same method on identical test material but under different conditions (different operators, different apparatus, different laboratories, and/or after different intervals of time). The measure of reproducibility is the standard deviation qualified with the term reproducibility as reproducibility standard deviation. In some contexts reproducibility may be defined as the value below which the absolute difference between two single test results on identical material obtained under the above conditions may be expected to lie with a specified probability. Note that a complete statement of reproducibility requires specification of the experimental conditions which differ. 

With the exception of antimicrobial preservatives and antioxidants (see below) and coloring matter (for which an identity test should be available), it is not normally necessary to test for the presence of excipients in finished products. 

Method performance study All laboratories follow the same written protocol and use the same test method to measure a quantity (usually concentration of an analyte) in sets of identical test samples. The results are used to estimate the performance characteristics of the method, which are usually within-laboratory- and between-laboratory precision and - if relevant - additional parameters such as sensitivity, limit of detection, recovery, and internal quality control parameters (IUPAC Orange Book [1997, 2000]). 

The topics of polymorphism and pseudopolymorphism dominate the majority of publications that deal with utilizing infrared spectroscopy for the physical characterization of pharmaceutical solids. Typically, in each of the publications, IR spectroscopy is only one technique used to characterize the various physical forms. It is important to realize that a multidisciplinary approach must be taken for the complete physical characterization of a pharmaceutical solid. Besides polymorphism, mid- and near-IR have been utilized for identity testing at the bulk and formulated product level, contaminant analysis, and drug-excipient interactions. A number of these applications will be highlighted within the next few sections. 

Repeatability Precision under repeatability conditions, i.e. conditions where independent test results are obtained with the same method on identical test items in the same laboratory by the same operator using the same equipment within short intervals of time. 

The physicochemical and other properties of any newly identified drug must be extensively characterized prior to its entry into clinical trials. As the vast bulk of biopharmaceuticals are proteins, a summary overview of the approach taken to initial characterization of these biomolecules is presented. A prerequisite to such characterization is initial purification of the protein. Purification to homogeneity usually requires a combination of three or more high-resolution chromatographic steps (Chapter 6). The purification protocol is designed carefully, as it usually forms the basis of subsequent pilot- and process-scale purification systems. The purified product is then subjected to a battery of tests that aim to characterize it fully. Moreover, once these characteristics have been defined, they form the basis of many of the QC identity tests routinely performed on the product during its subsequent commercial manufacture. As these identity tests are discussed in detail in Chapter 7, only an abbreviated overview is presented here, in the form of Figure 4.5. 

Determination in combination products a. General. Identity tests 83,86,103,104,105,... 

Brustier and coworkers utilized the Adamkiewicz-Hopkins-Cole reaction as an identity test for gramicidin121. The test detects the indole ring structure of the tryptophane residue. 

Fischbach and Levine described the use of Ehrlich s reagent as an identity test for gramicidin125. 

Guven and Ozsari reported some thin layer systems to use as identity tests for antibiotics including gramicidin190. McGilveray and Stickland described two thin layer chromatographic systems to use to identify several antibiotics including gramicidin191. 

Table 9 lists a number of colorimetric tests which have been used as identity tests for neomycin. No one test, however, has been demonstrated to be specific for neomycin and it is thus also advisable to establish the absence of other chemically similar antibiotics by suitable means. 

XRPD identity test criteria for mandelic acid... 

TLC and HPTLC can be used for both qualitative and quantitative studies. Five examples where TLC can be utilized qualitatively are discussed in this chapter and include reaction completion, identity testing, Rf determination, overlapping experiments, and TLC/HPLC correlation experimentation. 

Another common qualitative TLC test in the pharmaceutical industry is identity testing. A standard is applied to the plate side by side with the extracted sample, such as a tablet. The plate is developed in mobile phase and dried, then detected in accordance with the validated procedure. If the Rf value of the sample is consistent with that of the standard, then they are said to be of the same entity, and thus meet the identity test as shown in Fig. 13.15. 

In summary, TLC analysis plays a critical role in the drug development process. Many instruments are available, and the technique is used for both quantitative and qualitative testing. i f determination, identity testing, and stability testing are just a few ways to utilize TLC. 

The procedure used to determine whether a given result is unacceptable involves running a series of identical tests on the same sample, using the same instrument or other piece of equipment, over and over. In such a scenario, the indeterminate errors manifest themselves in values that deviate, positively and negatively, from the mean (average) of all the values obtained. Given this brief background, let us proceed to define some terms related to elementary statistics. 

Repeatability The absolute difference between two single test results found on identical test materials by one operator using the same apparatus within the shortest feasible time interval will exceed the repeatability value r in not more than 5% of the cases. 

All purity specifications normally list identity tests, an assay, further criteria like loss on drying, general maximum levels for heavy metals and substance-specific limits of byproducts. 

Materials Required Standard chlortertracyline sterilized media (as described above) 1 L authentic and pure strain of microorganism Staphylococcus aureus (NCTC 6571) formaldehyde solution (34-37% w/v) 10 ml matched identical test tubes 20 ... 

Procedure Distribute into identical test-tubes an equal volume of standard tetracycline solution and the sample to be examined (having presumed equal concentrations) and add to each tube an equal volume of inoculated nutrient medium (for instance 1 ml of the solution and 9 ml of the medium). Prepare at the same time two control tubes without the chlortetracycline, one containing the inoculated medium and the other identical with it but treated immediately with 0.5 ml of formaldehyde solution. These tubes are used to set the optical apparatus employed to measure the growth. 

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