Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 7 (5), 479-89

Increasing Speed and Throughput When Using HPLC-MS/MS Systems for Drug Metabolism and Pharmacokinetic Screening

Affiliations
Review

Increasing Speed and Throughput When Using HPLC-MS/MS Systems for Drug Metabolism and Pharmacokinetic Screening

Yunsheng Hsieh et al. Curr Drug Metab.

Abstract

Both combinatorial chemistry and parallel synthesis provide a valuable means for the production of large numbers of compounds with diverse molecular architectures that become available for various drug discovery experiments. In both the lead optimization and lead selection stages, one requirement that is common for many processes is the need for bioanalytical support. This review summarizes current high throughput strategies and efficient methodologies that are employed for drug metabolism and pharmacokinetic (DMPK) screens for a series of drug discovery compounds. For these types of assays, high performance liquid chromatography coupled to a tandem mass spectrometer (HPLC-MS/MS) has now become the technique of choice. The major high throughput strategies including sample reduction and cassette dosing are discussed. The methods for increasing the speed of HPLC-MS/MS-based analyses, such as fast chromatography, direct sample injection, parallel technologies and combined ionization interfaces are also presented in this review. In addition, the special challenges when performing HPLC-MS/MS bioanalysis, such as the choice of ionization sources, matrix ionization suppression and the potential for endogenous interferences, are addressed.

Similar articles

See all similar articles

Cited by 4 PubMed Central articles

MeSH terms

Substances

Feedback