Category I methods

The importance of methods to predict log P from chemical structure was described in Chapter 14, which is focused on fragment- and atom-based approaches. In this chapter property-based approaches are reviewed, which comprise two main categories (i) methods that use three-dimensional (3D) structure representation and (ii) methods that are based on topological descriptors. 

The newly developed techniques fall into two categories, (i) methods of measuring both the flux and the energy of the secondary neutrons, and (ii) methods of measurement of the y-rays emitted by the excited states of the residual nucleus. The latter are useful in the determination of the level scheme for the residual nucleus usually both methods are needed to elucidate quantitatively the whole sequence of events. 

Apart from polyplexes, various nanoscale assemblies of cationic polysaccharides are also proposed to promote the surface-mediated delivery of DNA to cells. These approaches are classified into one of two broad categories (i) methods based upon the physical adsorption of preformed polyplex on polymeric surfaces like PLGA or collagen films and these polyplex functionalized films promoted surface-mediated transfection of cells in vitro and in vivof (ii) methods for layer-by-layer adsorption of DNA and cationic polymers on surfaces to fabricate multilayered thin films. Recently, degradable carbohydrate-based nanogels were proposed for codelivery of pDNA and therapeutic proteins. These systems were designed to possess stimuli-sensitive characteristics where the temperature-sensitive property of nanogels allowed the facile encapsulation of biomaterials, while... 

Category II (Benchmark method) A category II method is designated as the benchmark method in cases where category I methods cannot be used. It should be selected from category III methods (as defined below). Such methods should be recommended for use in cases of disputes and for calibration purposes. 

While there are plenty of methods to predict 1-octanol-water partition coefficients, logP (see Chapters 14 and 15), the number of approaches to predict 1-octanol-water distribution coefficients is rather limited. This is due to a lower availability of log D data and, in general, higher computational complexity of this property compared to that of log P. The approaches to predict log D can be roughly classified into two major categories (i) calculation of log D at an arbitrary pH and (ii) calculation of log D at a fixed pH. 

Transition-metal oxides and their mixtures are widely employed in numerous industrial applications, especially as cathode materials for batteries and fuel cells [1,2], Practice poses certain well-known requirements to oxide materials, first of all, to uniformity of the size distribution of particles, to homogeneity of mixed oxides, etc. To meet these demands, two broad categories of methods are now in use, vs (i) mechanical methods and (ii) chemical methods. 

In order to predict pollutant chemodynamics of COMs and/or their leachates, the transport parameters involved in the governing sets of equations that describe the transport process need to be defined accurately [1]. In general, methods used to calculate the transport parameters fall into two broad categories, i. e., steady and transient states. 

Methods for the quantitation of major components of bulk drug substances or APIs, including preservatives, in finished drug products are classified in Category I. Assay and content uniformity methods fall into this category. These methods demonstrate that the label claim of the drug... 

Numerous methods have been developed for attaching ligands to the surface of liposomes for reviews, see Refs. (3,6 ). For peptides, they fall into two major categories (i) covalent coupling of the peptides to preformed liposomes that contain functionalized hydrophobic anchors such as, e.g., derivatives of phos-phatidylethanolamine (PE) or (ii) incorporation of lipopeptides, obtained by conjugation of peptides to hydrophobic anchors (fatty acids, phospholipids), into liposomes either during the preparation of the vesicles or by postinsertion into preformed vesicles. In this section, we will briefly discuss these techniques and focus on the ones we have been using in our own work. 

The USP requirements for assay validation are very close to the ICH proposal. Here, three categories are distinguished. Category I corresponds to ICH assay, category II corresponds to ICH determinations of impurities. The additional category III includes analytical methods for the determination of performance characteristics (e.g., dissolution, drug release). For this category, the ICH assay characteristics are always sufficient. The objective of the analytical procedure... 

The methods for the preparation of dialkyl peroxides can in principle be divided into three categories (i) acid- or base-catalyzed, (ii) metal-catalyzed and (iii) photochemical. 

The use of skin permeation enhancers in combination for synergistic effects has been studied in the transdermal literature (70). Such synergistic methods can be grouped in three categories (i) combination of two physical methods, e.g., ultrasound and iontophoresis (71-75) (ii) combination of a physical method with a chemical enhancer, e.g., use of ultrasound with sodium lauryl sulfate or isopropyl myristate (76-80) and (iii) combination of two chemicals, e.g., terpenes and propylene glycol (46,81-88). Numerous studies have been published on using combination of two physical methods or use of a physical method in conjunction with a chemical enhancer. Use of a physical method, by itself or in combination with another physical method, increases application cost for delivery purposes as mentioned before. In addition, there are unexplored safety and membrane recovery issues associated with these methods. A few reports have also been published on the use of a mixture of chemical enhancers for enhancing transdermal delivery. Typically, such studies use... 

Cyclopropanes occur among several classes of natural products, they have a number of commercial applications, and they serve as useful synthetic intermediates leading to other classes of cyclic and acyclic compounds. Methods for the synthesis of cyclopiopanes have been the subject of several earlier reviews.1 The principal methods may be divided into two broad categories (i) addition of a one-carbon... 

The efficiency of the combined method has been well demonstrated, particularly in the preparations of phosphaethenes (R1P=CR2R3). The synthetic routes to phosphaethenes can be classified into three major categories, i.e. the T, 2-elimination method , the condensation method , and the 1,3-silyl migration method (Scheme l)8. Among variations of the condensation method is included the addition-elimination method using, for example, bis(trialkylsilyl)phosphines and carbonyl compounds (Scheme 2). 

Category I Authorized compounds on positive lists with very low restrictions, for instance at or very close to the analytical detection limit. In this highly challenging situation the analytical method has to fulfil its classical task, which is to determine the target concentration as accurately as possible and the full extent of validation work is necessary. It is obvious that this does not deserve further explanation, as compromise with respect to the required precision data is not acceptable. 

Category I Analytical methods for quantitation of major components of food additives or processing aids (including preservatives). 

We shall divide these molecules into two categories (i) molecules with one large amplitude motion (inversion) which will be dealt with in Section 6.1 (ii) molecules with inversion and internal rotation (Section 6.2). Only such molecules will be considered, where the inversion barrier is low enough that inversion splittings can be resolved by microwave or infrared spectroscopy. As for the pyramidal inversion with higher barriers, description of the methods for determination of the barrier heights and the chemical consequences of the existence of the so-called invertomers, the reader is referred to review papers ... 

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