Sample type pharmaceutical

Quantitative voltammetry has been applied to a wide variety of sample types, including environmental samples, clinical samples, pharmaceutical formulations, steels, gasoline, and oil. 

IEC continues to have numerous applications to the detection and quantification of various inorganic ions.1 1 This is particularly true in water analysis.5-14 Inorganic ions in a variety of other sample types, such as food and beverages,1518 rocks,19-23 biological fluids, (blood, urine, etc.),24-31 pharmaceutical substances,32 33 concentrated acids,34 alcohols,35 and cleanroom air36 have also been analyzed by IEC. IEC has also been employed in isotopic separation of ions,37 including the production of radioisotopes for therapeutic purposes.3839 Typical IEC sample matrices are complex, and may contain substances that interfere with measurement of the ion(s) of interest. The low detection limits required for many IEC separations demand simple extraction procedures and small volumes to avoid over-dilution. Careful choice and manipulation of the eluent(s) may be needed to achieve the desired specificity, especially when multiple ions are to be determined in a single sample. 

Major applications of modern TLC comprise various sample types biomedical, pharmaceutical, forensic, clinical, biological, environmental and industrial (product uniformity, impurity determination, surfactants, synthetic dyes) the technique is also frequently used in food science (some 10% of published papers) [446], Although polymer/additive analysis takes up a small share, it is apparent from deformulation schemes presented in Chapter 2 that (HP)TLC plays an appreciable role in industrial problem solving even though this is not reflected in a flood of scientific papers. TLC is not only useful for polymer additive extracts but in particular for direct separations based on dissolutions. 

IR is one of three forms of vibrational spectroscopy that is in conunon use for process analytical measurements the other two being near-lR (NIR) and Raman. Each one of these techniques has its pros and cons and the ultimate selection is based on a number of factors ranging from sample type, information required, cost and ease of implementation. The sample matrix is often a key deciding factor. NIR has been the method of choice for many years within the pharmaceutical industry, and sample handling has been the issue, especially where solid products are involved. IR is not particularly easy to implement for the continuous monitoring of solid substrates. However, often there is no one correct answer, but often when the full application is taken into account the selection becomes more obvious. In some cases very obvious, such as the selection of IR for trace gas analysis - neither NIR nor Raman is appropriate for such applications. 

The aim of validation of an analytical procedure is to demonstrate that the method employed in any product testing, such as the identification, control of impurities, assay, dissolution, particle size, water content, or residual solvents, is validated in the most important characteristics. Identification tests, quantitative tests for impurities content, limit tests for control of impurities, and quantitative tests of the active moiety in samples of pharmaceutical product are the most common types of analytical procedures that validation addresses [1]. 

Today, in the pharmaceutical industry, there exists a variety of technologies to which either partial or full automation of quantitative bioanalytical steps can make the process higher throughout. However, choosing the appropriate technology to automate requires an evaluation of several parameters, including number of samples, type of samples, and time required to automate in comparison to nonautomated work flow. 

Liquid chromatography/mass spectrometry (LC/MS)-based techniques provide unique capabilities for pharmaceutical analysis. LC/MS methods are applicable to a wide range of compounds of pharmaceutical interest, and they feature powerful analytical figures of merit (sensitivity, selectivity, speed of analysis, and cost-effectiveness). These analytical features have continually improved, resulting in easier-to-use and more reliable instruments. These developments coincided with the pharmaceutical industry s focus on describing the collective properties of novel compounds in a rapid, precise, and quantitative way. As a result, the predominant pharmaceutical sample type shifted from nontrace/pure samples to trace mixtures (i.e., protein digests, natural products, automated synthesis, bile, plasma, urine). The results of these developments have been sig-... 

Figure 1.1 Structure analysis matrix that illustrates pharmaceutical analysis preferences for four specific sample types nontrace/pure nontrace/ mixture trace/pure and trace/mixture. (Courtesy of Milestone Development Services, Newtown, Pa., USA.)...

In a review of the performance of combinatorial chemicals alongside natural product extracts in several biochemical assays, there no comprehensive significant differences (Table 1). Natural products and combinatorial chemicals were screened in three different biochemical assays of current pharmaceutical relevance. In one assay, natural products resulted in more confirmed active samples than combinatorials. In another assay, the reverse was true. In a third assay, both sample types performed about the same. In the majority of assays formatted for high throughput, both combinatorial chemicals and natural products will provide adequate numbers of active samples for drug candidate lead identification programs. There is a perception however, that for biochemical assays for which combinatorial chemicals fail to produce a significant number of active samples, natural products are likely to provide some possibilities. 

Like gas chromatography (GC), HPLC employs a chromatographic column for the separation. It differs from GC in that the sample components need not be volatile and stable at elevated temperatures, they must only be soluble in a suitable single-component or mixed solvent. Various modes of HPLC can be applied to the analysis of a large variety of sample types containing non-polar, moderately or strongly polar and ionic compounds, either simple species or high-molecular mass synthetic polymers or biopolymers. These features of HPLC are especially useful in pharmaceutical and clinical analysis. 

For pharmaceutical applications, the term bioanalysis refers to quantitative determination of a drug or its metabolites in a biological matrix. Although this term has traditionally been used to describe the analysis of in vivo samples (i.e., plasma or serum), current use of the term encompasses a broader range of applications that include the analysis of in vitro samples. Under this broader dehnihon, possible bioanalytical sample types can range anywhere from transport media to tissue homogenate. 

This chapter provides an overview of modern HPLC method development and discusses approaches for initial method development (column, detector, and mobile phase selection), method optimization to improve resolution, and emerging method development trends. The focus is on reversed-phase methods for quantitative analysis of small organic molecules since RPLC accounts for 60-80% of these applications. Several case studies on pharmaceutical impurity testing are presented to illustrate the method development process. For a detailed treatment of this subject and examples of other sample types, the reader is referred to the classic book on general HPLC method development by L. Snyder et al.1 and book chapters2,3 on pharmaceutical method development by H. Rasmussen et al. Other resources include computer-based training4 and training courses.5... 

Table 1 lists types of samples that are typically found in the pharmaceutical analytical chemistry lab. Different dosage forms and sample types represent different types of chemical mixtures and offer a different set of sample preparation problems. Pharmaceuticals are necessarily formulated as chemical mixtures to achieve the desired physiological effect. The purposes of inactive ingredients are varied see Table 2. 

Perhaps the most common type of problem encountered in the analytical lab is a quantitative analysis. Examples of typical quantitative analyses include the elemental analysis of a newly synthesized compound, measuring the concentration of glucose in blood, or determining the difference between the bulk and surface concentrations of Cr in steel. Much of the analytical work in clinical, pharmaceutical, environmental, and industrial labs involves developing new methods for determining the concentration of targeted species in complex samples. Most of the examples in this text come from the area of quantitative analysis. 

---