Midazolam is a CNS depressant that is commonly used as a sedative prior to surgical or other  medical procedures. It is a controlled substance which, when abused, can cause serious side  effects including amnesia, respiratory depression or even death. The primary metabolite of  midazolam, 1-hydroxymidazolam, is also a biologically active sedative with similar potency as  the unaltered drug.1 It is known that in humans the 3A isozymes of cytochrome P450 are  responsible for this oxidative biotransformation.2 In order to monitor plasma concentrations of  midazolam and 1-hydroxymidazolam, either for patients treated with this sedative or for  profiling cytochrome P450 drug-drug interactions, 3–6 a reliable, sensitive and selective  LC/MS/MS method is required.

The TSQ Quantum line of triple quadrupole mass spectrometers offers  the unique capability of highly-selective reaction monitoring (H-SRM). H-SRM is superior to  selective reaction monitoring (SRM) given that H-SRM provides higher analyte selectivity by means of improved mass resolution of a precursor ion with Q1 while maintaining high transmission efficiency. The TSQ Quantum family achieves this increased selectivity on its massresolving  quadrupoles by employing hyperbolic-faced rods as opposed to round rod used by all other  commercially available quadrupole mass spectrometers.

The practical advantage H-SRM provides is  the ability to remove isobaric chemical noise thereby increasing the signal-tonoise (S/N), which  translates to improved limits of quantitation (LOQs) and higher confidence in the quantitation results. Furthermore, data acquisitions using H-SRM can be executed by simply changing the Q1 peak setting in the Instrument Setup in the Xcalibur™ data system.

To vew the complete application note, please download the PDF file at the left of this page.