Book123

Preface

PHARMACEUTICAL ANALYSES ARE PERFORMED in a variety of situations

that range from the assay of a new chemical entity in the presence

of optical isomers and other related compounds (e.g., intermediates,

byproducts, degradation products, and metabolites) to complex determination

at trace or ultratrace concentrations in various matrices. Chromatography

plays a major role in pharmaceutical analyses because it provides

selectivity and detectability. Chromatography of Pharmaceuticals,

which is intended to serve as a reference for pharmaceutical researchers,

surveys the use of chromatography in the analysis of pharmaceuticals.

A number of analytical methods are discussed in great detail. These

include gas chromatography (GC), capillary GC, GC-mass spectrometry

(MS), high-performance liquid chromatography (HPLC or LC), L C - L C -

ultraviolet (UV) detection, LC-MS, LC-MS-MS, capillary electrophoresis

(CE), robotics, and preparative separations. Alternative strategies

for analyzing pharmaceutical compounds are also discussed, along

with the popular reversed-phase HPLC methods.

The purity of recombinant proteins is of paramount importance in

drug therapy. Impurities in these drugs can be potentially unsafe and can

include endotoxins, DNA, and host-cell proteins. The ability to detect,

identify, and quantify impurities is an ongoing challenge for the analyst.

This book provides an overview of the current chromatographic methods

used to analyze host-cell protein impurities.

Biochemical interactions, such as those of binding proteins with

ligands, enzymes with substrates, antibodies with antigens, and receptors

with hormones, are characterized by a high degree of specificity. In these

cases, specificity is achieved by the formation of noncovalent complexes in

which at least one of the reacting species is macromolecular. Such biospecific

interactions form the basis of a range of chromatographic techniques,

including protein-binding assays. These assays for determining

metabolites in biological samples are discussed at length.

A suitable method for the analysis of small samples in biological

matrices is exemplified by the determination of ceftibuten in tracheal and

bronchial secretion or in middle-ear fluid. Only a small volume (<30 /zL)

of these fluids is generally available. Trace-ultratrace LC-LC-UV

assays are included for these samples. In addition, an LC-LC-MS

method is discussed for determination of the drug in sputum samples, for

which the other methods have proved unsuccessful.