Identification assay

Most chemists tend to think of infrared (IR) spectroscopy as the only form of vibrational analysis for a molecular entity. In this framework, IR is typically used as an identification assay for various intermediates and final bulk drug products, and also as a quantitative technique for solution-phase studies. Full vibrational analysis of a molecule must also include Raman spectroscopy. Although IR and Raman spectroscopy are complementary techniques, widespread use of the Raman technique in pharmaceutical investigations has been limited. Before the advent of Fourier transform techniques and lasers, experimental difficulties limited the use of Raman spectroscopy. Over the last 20 years a renaissance of the Raman technique has been seen, however, due mainly to instrumentation development. 

The pharmaceutical industry comprises the largest segment, roughly 15 to 20%, of the infrared (IR) market. Modern mid-infrared instrumentation consists almost exclusively of Fourier transform (FT) instruments. Because of its ability to identify molecular species, FT-IR is routinely used as an identification assay for raw materials, intermediates, drug substances, and excipients. However, the traditional IR sample preparation techniques such as alkali halide disks, mulls, and thin films, are time-consuming and not always adequate for quantitative analysis. 

Capillary electrophoresis (CE) has become a valuable technique in the analytical toolbox for pharmaceutical analysts. CE methods have been successfully applied for identification, assay, purity determination, and chiral separation. ICH guidelines should be followed in meeting regulatory approval if CE methods are used in a registration dossier. Here, the validation parameters required for different analytical procedures are described and a comprehensive overview of CE validation studies presented in literature is given. 

CE is an important separation technique within the field of pharmaceutical analysis. CE may be an attractive choice as analytical procedure for identification, assay, or (chiral) purity determination. In addition, CE may provide distinct advantages over existing pharmacopoeial... 

CE is applied to two major categories of quality release testing identity and impurity testing. Identification assays are intended to ensure the unique identity of an analyte in the sample. This is normally achieved by comparison of a property of the sample (e.g., spectrum, chromatographic behavior, chemical reactivity, etc.) to that of a reference standard. As shown in Figure 9, CZE can be used to determine identity for monoclonal antibodies and proteins based on their unique electrophoretic profile. 

TLC Dissolve in 0.1 /VHC1 uae within 10 min Silica MeOH-pyridine-CHCI3-H 0 (90 10 80 10) Ninhydrin USP 23, p. 100, identification, assay by HPLC, oral suspension tablets with clavulanate. assay by HPLC. p. 103 also. BP. P 31 [4] [5]... 

Haff LA, Smirnov IP. Single-nucleotide polymorphism identification assays using a thermostable DNA polymerase and delayed extraction MALDI-TOF mass spectrometry. Genome Res 1997 7 378-388. 

Revision Description corrected Assay limit of d-maltitol revised entire Identification, Assay, and Reducing Sugars tests provided. 

USP 23, pp. 106-9, identification, assay HPLC, p. 107, with probenecid capsules assay by HPLC. p. 111. with sulbactam, p. 113 with cloxacillin [171] UV [174]... 

When it comes to the practical details of how bioinformatics can speed the process of drug discovery, it is reasonable to ask what sorts of data could be valuable in that process. The stages of the drug discovery process where bioinformatics makes an impact are target identification, assay selectivity panel selection, and integration throughout the as-... 

In Norway, Wieders Farmasoytiske A/S received approval for the use of NIR as an alternative method for identification, assay, and determination of moisture content of paracetamol (acetaminophen) tablets. The Norwegian Medicines Control Authority approved the method in December 1996. 

MS-based substrate identification assays of tailoring enzymes depend on whether the biosynthetic substrate is T domain bound or not. If the biosynthetic substrate is T domain bound, the predicted native substrate is loaded on the T domain and the mass change upon the tailoring reaction is detected by ESI—FTMS. If the biosynthetic substrate is non-T domain bound, conversion of the predicted native substrate by tailoring reaction can be detected by low-resolution MS. Biosynthetic substrate tolerance assays for tailoring enzymes are conducted in a one-assay-one-substrate approach like substrate identification assays but with alternative biosynthetic substrates. 

Figure 16 Lipidation of daptomycin. (a) Role of DptE and DptF in daptomycin lipidation. DptE adenylates decanoic acid and tethers it on T domain DptF for insertion into daptomycin. (b) DptE substrate identification assay (observed and calculated mass shifts from holo DptF characterized by ESI-FTMS).

Numerous methods are required to characterize drug substances and drug products (Chapter 10). Specifications may include description identification assay (of composite sample) tests for organic synthetic process impurities, inorganic impurities, degradation products, residual solvents, and container extractables tests of various physicochemical properties, chiral purity, water content, content uniformity, and antioxidant and antimicrobial preservative content microbial tests dissolution/disintegration tests hardness/friability tests and tests for particle size and polymorphic form. Some of these tests may be precluded, or additional tests may be added as dictated by the chemistry of the pharmaceutical or the dosage form. 

Universal test A test that is considered potentially applicable to all new drug substances, or all new drug products for example, appearance, identification, assay, and impurity tests. 

Mid-infrared (MIR) spectroscopy MIR spectroscopy (frequency range 2.5-25nm or 4000 00 cm ) is a popular technique for identification assays (chemical identity) of dmg substances in pharmacopoeias. The fact that different solid-state forms exhibit different MIR spectra represents rather a problem for such purposes. Thus, in the case that the spectmm of a compound, whose identity needs to be determined or confirmed, is different than that of the reference compound, pharmacopoeias suggest either to record the spectra in solution or to recrystallize both the substance and the reference using the same method before recording their solid-state spectra. 

Conjugated Estrogens, USP Identification assay, content of 17a-dihydroequilin, 17j8-dihydroequilin, and 17 alpha-estradiol (concomitant components)— C 0.25... 

---