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Analytical requirements Chromatographic methods

المؤلف:  Sue Jickells , Adam Negrusz (Editors)

المصدر:  Clarkes Analytical Forensic Toxicology

الجزء والصفحة:  p252-253

2026-10-19

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Analytical requirements

Chromatographic methods

Chromatographic methods are flexible and adaptable to a wide range of compounds. Methods for new compounds can be devised relatively quickly in most cases, compared to immunoassays for which development times can be significant, particularly if a new antiserum must be raised. Chromatographic techniques frequently allow quantification of a range of related compounds in a single run, which has advantages when a number of drugs are prescribed together (e.g. anticonvulsants) or when separate quantification of a drug and its active metabolites is required. The combination of flexibility, specificity and sensitivity makes chromatographic techniques the method of choice for many toxicological applications. However, for TDM purposes they have a number of disadvantages. In comparison to immunoassays they are slower and more labour intensive, frequently demanding a significant level of technical expertise. Sample throughput is usually lower than for automated immunoassays, and sample volume is often higher, which is a particular disadvantage for paediatric applications. Sample preparation is also more laborious, since extraction or formation of a chemical derivative may be required before the chromatographic step. Both gas chromatography (GC) and high-performance liquid chromatography (HPLC) still have a role, but the previously dominant position of GC in clinical work has steadily been eroded and is probably only relevant in association with mass-spectrometric (MS) detection. HPLC and LC-MS are now the chromatographic methods of choice for most TDM applications There are different types of mass spectrometry: ion-trap and quadrupole, with hybrids and varying geometries. In recent years, the cost of instruments has fallen dramatically, and LC MS/MS (LC–tandem MS) is becoming the stand ard technique for some routine analytes (e.g. the immunosuppressant sirolimus). The flexibility and ease of sample preparation of LC-MS/MS has led to its adoption for a number of drug assays which are not amenable to standard LC for reasons such as poor sensitivity and lack of an available chromophore for UV detection.