Orbitrap Illustration

Anticancer drugs quantitation

Quantitative analysis of drugs in various body fluids, such as plasma, serum, and cerebrospinal fluid (CSF), is conducted in many research laboratories. SRM analysis using a triple quadrupole LC-MS/MS system has been routinely employed for quantitative analysis. Although, in most cases, SRM offers the required sensitivity and specificity, it suffers from interferences and a lack of robustness and needs expert MS users. High-resolution, accurate mass (HR/AM) mass spectrometry based on Orbitrap™ technology offers an attractive alternative with unique benefits of specificity, sensitivity and, more importantly, ease of use.
Here we describe the quantitative workflow solutions using the Thermo Scientific Exactive Plus system for the following classes of drugs:
  • Immunosuppressant drugs
  • Anticancer drugs
  • Antifungal drugs

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Workflow Overview for Anticancer Drugs Quantitation

Quantitative analysis of protein kinase inhibitors such as Dasatinib, Imatinib, Nilotinib, Sorafenib and Sunitinib is done in research for various purposes. While selected reaction monitoring (SRM)-based analysis is routinely used for quantitation, high-resolution Full Scan MS or SIM offers a simpler alternative without any drawbacks.
The workflow described here uses simple Full Scan MS at 70,000 FWHM resolution. The data is acquired in Full Scan mode and the quantitation is performed by using extracted ion chromatograms with a 3 ppm window around the m/z of interest. This application demonstrates the capability of the Thermo Scientific Exactive Plus MS coupled to a uHPLC system for quantitative analysis of the five above-mentioned drugs.  For Dasatinib and Sunitinib the LLOQ was 1 ng/mL and the ULOQ was 500 ng/mL. For Imatinib, Nilotinib, and Sorafenib the LLOQ was 20 ng/mL and the ULOQ was 10,000 ng/mL.



Quan / Qual Analyses in Clinical Research using a Second Generation Exactive High Resolution Mass Spectrometer

Rochat B.
ASMS 2012 Presentation

Comparison between a high-resolution single-stage Orbitrap and a triple quadrupole mass spectrometer for quantitative analyses of drugs

Henry H, Sobhi HR, Scheibner O, Bromirski M, Nimkar SB, Rochat B.
Rapid Commun Mass Spectrom. 2012 Mar 15;26(5):499-509.