Direct analysis in real time-mass spectrometry for rapid quantification of five anti-arrhythmic drugs in human serum: application to therapeutic drug monitoring

Abstract Therapeutic drug monitoring (TDM) is necessary for the optimal administration of anti-arrhythmic drugs in the treatment of heart arrhythmia. The present study aimed to develop and validate a direct analysis in real time tandem mass spectrometry (DART–MS/MS) method for the rapid and simultaneous determination of five anti-arrhythmic drugs (metoprolol, diltiazem, amiodarone, propafenone, and verapamil) and one metabolite (5-hydroxy(OH)-propafenone) in human serum. After the addition of isotope-labeled internal standards and protein precipitation with acetonitrile, anti-arrhythmic drugs were ionized by DART in positive mode followed by multiple reaction monitoring (MRM) detection. The use of DART–MS/MS avoided the need for chromatographic separation and allowed rapid and ultrahigh throughput analysis of anti-arrhythmic drugs in a total run time of 30 s per sample. The DART–MS/MS method yielded satisfactory linearity (R2 ≥ 0.9906), accuracy (86.1–109.9%), and precision (≤ 14.3%) with minimal effect of biological matrixes. The method was successfully applied to analyzing 30 clinical TDM samples. The relative error (RE) of the concentrations obtained by DART–MS/MS and liquid chromatography-tandem mass spectrometry (LC–MS/MS) was within ± 13%. This work highlights the potential usefulness of DART for the rapid quantitative analysis of anti-arrhythmic drugs in human serum and gives rapid feedback in the clinical TDM practices.

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Therapeutic Drug Monitoring of the new targeted anticancer agents imatinib, nilotinib, dasatinib, sunitinib, sorafenib and lapatinib by LC tandem mass spectrometry

Journal of Chromatography B ◽

10.1016/j.jchromb.2009.04.045 ◽

2009 ◽

Vol 877 (22) ◽

pp. 1982-1996 ◽

Cited By ~ 127

Author(s):

A. Haouala ◽

B. Zanolari ◽

B. Rochat ◽

M. Montemurro ◽

K. Zaman ◽

...

Keyword(s):

Mass Spectrometry ◽

Therapeutic Drug Monitoring ◽

Tandem Mass Spectrometry ◽

Anticancer Agents ◽

Drug Monitoring ◽

Therapeutic Drug ◽

Tandem Mass

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Multiplex Liquid Chromatography-Tandem Mass Spectrometry Assay for Simultaneous Therapeutic Drug Monitoring of Ribavirin, Boceprevir, and Telaprevir

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00281-13 ◽

2013 ◽

Vol 57 (7) ◽

pp. 3147-3158 ◽

Cited By ~ 16

Author(s):

Manel Aouri ◽

Darius Moradpour ◽

Matthias Cavassini ◽

Thomas Mercier ◽

Thierry Buclin ◽

...

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Hepatitis C ◽

Therapeutic Drug Monitoring ◽

Tandem Mass Spectrometry ◽

Antiviral Therapy ◽

Drug Monitoring ◽

Reversed Phase ◽

Therapeutic Drug ◽

Tandem Mass

ABSTRACTNew directly acting antivirals (DAAs) that inhibit hepatitis C virus (HCV) replication are increasingly used for the treatment of chronic hepatitis C. A marked pharmacokinetic variability and a high potential for drug-drug interactions between DAAs and numerous drug classes have been identified. In addition, ribavirin (RBV), commonly associated with hemolytic anemia, often requires dose adjustment, advocating for therapeutic drug monitoring (TDM) in patients under combined antiviral therapy. However, an assay for the simultaneous analysis of RBV and DAAs constitutes an analytical challenge because of the large differences in polarity among these drugs, ranging from hydrophilic (RBV) to highly lipophilic (telaprevir [TVR]). Moreover, TVR is characterized by erratic behavior on standard octadecyl-based reversed-phase column chromatography and must be separated from VRT-127394, its inactive C-21 epimer metabolite. We have developed a convenient assay employing simple plasma protein precipitation, followed by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) for the simultaneous determination of levels of RBV, boceprevir, and TVR, as well as its metabolite VRT-127394, in plasma. This new, simple, rapid, and robust HPLC-MS/MS assay offers an efficient method of real-time TDM aimed at maximizing efficacy while minimizing the toxicity of antiviral therapy.

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