Drug analysis analytical techniques

Before the emergence of radioimmunoassay as an acceptable analytical technique, a number of other methods were employed for the analysis of drugs in the plasma. Prominent among these methods were thin-... 

It is earnestly believed that Pharmaceutical Drug Analysis will fulfill the entire requirements of both penultimate and final year students of B. Pharm., for their various courses in analytic chemistry in the universities. It may also help the post-graduate students in their compulsory paper on Modem Analytical Techniques to a great extent. 

LC/MS is the ultimate analytical technique, which combines the versatility of HPLC with the identification power of MS. The weak link in LC/MS has always been the interface which connects the liquid stream at atmospheric pressure to the high vacuum present inside the mass spectrometer. The development of several atmospheric pressure interfaces, electrospray and atmospheric pressure chemical ionization (APCI), has contributed to the tremendous success and popularity of LC/MS and LC/MS/MS in bioresearch, drug discovery, combinatorial analysis and pharmacokinetic assays. This topic is covered in more depth in a later chapter. 

Though in competition with other analytical techniques, CE has proven its potential and necessity to be used for the characterization of small-molecule pharmaceuticals. Due to the versatility of the system, CE can be applied for the determination of physicochemical properties, identification, purity and stability analysis, and cleaning verification of the drug substance, its precursors, process chemicals, the drug product, and its excipients. 

In Table 1, the typical validation parameters required for the different types of analytical procedures are listed. For all these analytical procedures CE might be an appropriate analytical technique. In fact numerous validated CE methods for pharmaceutical analysis have been described in literature during the last decade.In Table 2, an overview is listed of the ICH validation parameters included in several reported CE validation studies. Since chiral purity determination is an important application area of CE methods, this test is listed separately as a specific analytical procedure. In addition, the determination of drug counterions has been included as a separate application. This overview illustrates that in general the required validation parameters are addressed in reported CE validation studies. It should be noted, however, that the validation parameters included in Table 2 are not necessarily evaluated exactly according ICH requirements in the reported references. Many pharmaceutical companies apply a phase-related validation approach in which the depth of validation depends on the clinical phase of development of the product involved. 

Dedicated applications of capillary zone electrophoresis (CZE) coupled to MS are discussed, particularly in the field of drug analysis. Development of other capillary-based electrodriven separation techniques such as non-aqueous capillary electrophoresis (NACE), micellar electrokinetic chromatography (MEKC), and capillary electrochromatography (CEC) hyphenated with MS are also treated. The successful coupling of these electromigration schemes with MS detection provides an efficient and sensitive analytical tool for the separation, quantitation, and identification of numerous pharmaceutical, biological, therapeutic, and environmental compounds. 

The forensic scientist has multiple analytic techniques available. Some are screening tests that may not absolutely identify the chemical in question but narrow the number of possibilities. Subsequently, the analyst will perform confirmatory tests in which the chemical is positively identified. It is important to remember that even though the analysis may reveal the presence of a drug, there may be a legitimate reason for such a finding. We will discuss such examples in individual chapters. 

Analytical techniques have also been successfully developed to identify and quantify these compounds. The scientific literature is rich in descriptions of the various methods. Several chapters in a recently published multiauthor book (7-13) and articles (6,14,15) have provided excellent reviews of the methodologies available for the analysis of antimicrobial drugs from biomatrices. 

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