Analysis of Novel Melphalan Hydrolysis Products Formed Under Isolated Lung Perfusion Conditions Using Liquid Chromatography/tandem Mass Spectrometry.

Analysis of novel melphalan hydrolysis products formed under isolated lung perfusion conditions using liquid chromatography/tandem mass spectrometry.

Rapid Commun Mass Spectrom. 2013 Apr 15; 27(7): 835-841
Boschmans J, de Bruijn E, Van Schil P, Lemière F

RATIONALE: Melphalan is a widely used cytotoxic agent in cancer treatments. This phenylalanine analog has been shown an effective drug in the treatment of breast cancer, multiple myeloma and melanoma of the extremities. A good knowledge of the drug’s degradation and metabolism are crucial for understanding its activity during cancer treatments. METHODS: The formation of hydrolysis products of melphalan is studied using ultra-performance liquid chromatography (UPLC) tandem mass spectrometry (MS/MS). Aqueous melphalan solutions were incubated at elevated temperatures and analyzed by UPLC/MS/MS. Two previously described hydrolysis products, mono- and dihydroxymelphalan (MOH and DOH), were formed in vitro and could be characterized during MS/MS and high-resolution experiments. RESULTS: Novel compounds with m/z values >500?Da were discovered. Comparison of the fragmentation patterns of these new molecules with those of MOH and DOH show great similarities. The higher masses are explained by the presence of two or more melphalan units. In total, more than 15 new hydrolysis products were found. Experiments were set up to study the formation and the chemical structures of these molecules. CONCLUSIONS: The hydrolysis of melphalan is studied in the scope of a phase II clinical trial (isolated lung perfusion, ILuP). Patient samples were screened for the presence of all documented and novel melphalan hydrolysis products. This study reports the formation of a new class of oligomeric compounds in both in vivo and in vitro samples. Copyright © 2013 John Wiley & Sons, Ltd. HubMed – drug


NIR-Triggered Anticancer Drug Delivery by Upconverting Nanoparticles with Integrated Azobenzene-Modified Mesoporous Silica.

Angew Chem Int Ed Engl. 2013 Mar 12;
Liu J, Bu W, Pan L, Shi J

Photomediated drug release: Silica-coated upconverting nanoparticles with mesopores modified by azobenzene molecules were synthesized. The azobenzene molecules make possible the release of the anticancer drug doxorubicin from the pore network of the mesoporous silica outer layer by irradiation with near-infrared (NIR) laser light. The release is regulated by the trans-cis photoisomerization of the azobenzene molecules. HubMed – drug


A Cutting-Edge View on the Current State of Antiviral Drug Development.

Med Res Rev. 2013 Mar 11;
De Clercq E

Prominent in the current stage of antiviral drug development are: (i) for human immunodeficiency virus (HIV), the use of fixed-dose combinations (FDCs), the most recent example being Stribild(TM) ; (ii) for hepatitis C virus (HCV), the pleiade of direct-acting antivirals (DAAs) that should be formulated in the most appropriate combinations so as to obtain a cure of the infection; (iii)-(v) new strategies (i.e., AIC316, AIC246, and FV-100) for the treatment of herpesvirus infections: herpes simplex virus (HSV), cytomegalovirus (CMV), and varicella-zoster virus (VZV), respectively; (vi) the role of a new tenofovir prodrug, tenofovir alafenamide (TAF) (GS-7340) for the treatment of HIV infections; (vii) the potential use of poxvirus inhibitors (CMX001 and ST-246); (viii) the usefulness of new influenza virus inhibitors (peramivir and laninamivir octanoate); (ix) the position of the hepatitis B virus (HBV) inhibitors [lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate (TDF)]; and (x) the potential of new compounds such as FGI-103, FGI-104, FGI-106, dUY11, and LJ-001 for the treatment of filoviruses (i.e., Ebola). Whereas for HIV and HCV therapy is aimed at multiple-drug combinations, for all other viruses, HSV, CMV, VZV, pox, influenza, HBV, and filoviruses, current strategies are based on the use of single compounds. HubMed – drug