Hplcmsms Overview

Electronics Repair Manuals

Schematic Diagrams and Service Manuals

Get Instant Access

HPLC-MS/MS has been described as the premier analytical tool for drug metabolism participation in the new drug discovery process and has been applied to a

Dmpk Flow Discovery

Fig. 13.2 Schematic diagram showing the various stages and the iterative steps involved in the lead optimization process from a DMPK perspective. This schematic represents the iterative process that is an important part of the lead optimization process. The in vitro and in vivo screens refer to DMPK assays. Reprinted from [12], with permission from Taylor and Francis Group.

Fig. 13.2 Schematic diagram showing the various stages and the iterative steps involved in the lead optimization process from a DMPK perspective. This schematic represents the iterative process that is an important part of the lead optimization process. The in vitro and in vivo screens refer to DMPK assays. Reprinted from [12], with permission from Taylor and Francis Group.

variety of DMPK samples [4, 6, 8, 9, 11, 23-27]. A description of HPLC-MS/MS principles and instrumentation can be found in Chapter 1 of this book as well as in some recent review articles and books [2, 3, 9, 11, 23, 26, 28-31]. Briefly, as shown in Fig. 13.3, HPLC-MS/MS systems combine an HPLC system with a mass spectrometer with the whole system under the control of a personal computer. While the most commonly used MS/MS system is the triple quadrupole mass spectrometer, there are now a variety of additional ''hybrid'' MS/MS systems that can be utilized for various drug discovery applications, including some DMPK applications. A discussion of various ''hybrid'' MS/MS systems can be found in Chapter 1 as well as in recent articles and other book chapters [9, 11, 32-38].

Schematic Diagram Hplc
Fig. 13.3 Elements of an HPLC-MS/MS system including the autosampler, the HPLC, a switching valve, the API ionization source and the MS/MS system. Typically, these are all controlled by a single PC that also serves as the data collection tool.

For the analysis of samples from discovery PK studies, the HPLC-MS/MS system will typically be based on a triple quadrupole mass spectrometer for the MS/ MS part of the system [4, 6]. The reason that a triple quadrupole mass spectrometer is commonly used for bioanalytical assays is because it has the capability of operating in the selected reaction monitoring (SRM) mode. In SRM, analyte molecules are ionized by the atmospheric pressure ionization (API) source and the first quadrupole (Q1) is used to select the analyte ion (typically this will be the protonated molecule); the analyte ion is then fragmented in the collision cell (Q2) and the selected product ion is monitored via the third quadrupole (Q3). This mode of operation and its high degree of selectivity was first reported by Brotherton and Yost [39] in 1983; SRM has been used in conjunction with the separation capabilities of HPLC to produce an analytical tool that can be utilized to produce high quality data in a high throughput environment (see Chapter 1 for more on this topic).

Was this article helpful?

0 0

Responses

Post a comment