Within the realm of pharmaceutical drug analyses, two techniques currently dominate the field. High‐performance liquid chromatography (HPLC) is at the forefront, followed somewhat distantly by gas chromatography (GC). HPLC is more prevalent than GC owing mainly to the heat‐labile nature of the majority of drug substances. Still GC continues to play a very active role. In comparison to HPLC and GC, combined, the frequency of use of other techniques is quite small. Perhaps the major reason for this is that chromatography not only involves qualitative and quantitative detection of targeted species, but also provides a medium for isolating these analytes from potential interfering impurities prior to measurement. The proficiency of this combination is unparalleled by any other blending of means to clean up a sample and detect the target compound. These more prominent techniques are often complementary, although each has its own strengths and limitations. General guidelines are given to assist the chromatographer to elect HPLC and/or GC for a particular separation. Considerations for choosing hardware type and sizes, solid support and bonded phase are presented. Particular emphasis is placed on the latest, which is of primary importance for obtaining rugged methods. The reader is directed towards optimum phase selection based on the compound of interest's functional group type, or by its drug activity classification (e.g. barbiturate, cardiovascular, etc.). Assistance in developing new methods frequently arises when starting with an existing published method for a compound with similar structure. This article provides 514 references for more in‐depth separation information. In addition, background knowledge on bonded‐phase chemistry, chromatographic modes of separation, approaches to chromatographic chiral drug discrimination and processes for developing rugged methods is contributed.
