Simultaneous determination of gemcitabine, taxol, cyclophosphamide and ifosfamide in wipe samples by high-performance liquid chromatography/tandem mass spectrometry: protocol of validation and uncertainty of measurement

Measurable levels of anticancer agents are still detected on work surfaces in health-care settings. However, application of recent guidelines for the protection of workers' safety and health has resulted in lowered contamination levels. To assess occupational exposure to antineoplastic agents, very sensitive and specific procedures for environmental sampling and analysis are therefore needed. In the present study an assay for simultaneous determination of gemcitabine, taxol, cyclophosphamide, and ifosfamide in wipe samples, using two internal standards (trofosfamide and cephalomannine), was developed and validated by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). Solid-phase extraction (SPE) was used for sample concentration and cleanup. The assay was found to be linear up to 1000 ng/wipe, with limits of quantitation of 25.0 ng/wipe for gemcitabine and taxol, and 12.5 ng/wipe for cyclophosphamide and ifosfamide. In order to investigate the effectiveness of the surface sampling, removal efficiency tests were repeated on different types of surfaces. Recovery rates of between 62 and 81% were obtained at two contamination levels (50.0 and 250 ng/100 cm2). Precision and trueness were determined on three different days. The within-day precision was found to be always less than 12.1% for all the analytes. The overall precision, expressed as relative standard deviation (RSD), was always less than 9.4%. Recoveries varying from 75.0 (gemcitabine) to 95.0% (taxol) were obtained at three levels. In order to obtain a quantitative indication of the quality of the result, the overall uncertainty of measurement (UOM) was evaluated according to the EURACHEM/CITAC guide. The relative combined uncertainty was found to be always less than 9.5%. The relative expanded uncertainty was also calculated, at three contamination levels.     

Do collisions inside the collision cell play a relevant role in CID‐LIFT experiments?

Collision experiments are a valid approach to characterize the ionic species generated by matrix assisted laser desorption ionization (MALDI). When a time-of-flight analyzer is employed, three different approaches are available for these experiments: the postsource decay (PSD), the LIFT and the MALDI-TOF/TOF. The last two are of particular interest because of the overcoming of the PSD problems related to mass calibration of the product ion spectra. Experiments performed by LIFT on linear or cyclic peptides, in presence or in absence of collision gas in the collision cell, gave evidence of an unexpected behavior: the two spectra were practically superimposable, and in the former case only a few new fragmentation channels were activated with low yield. These results mean that the selected ion exhibits a large amount of internal energy, capable of promoting fragmentation processes in the time window corresponding to the flight time between ion source and the acceleration electrode placed after the collision cell. Experiments performed by varying the plume density show that this internal energy uptake occurs in the expanding plume, through multiple collisions. The LIFT data have been compared with those achieved by collisions of ESI-generated [MH](+) ions of angotensin II performed under 'in-source' conditions and by triple-quadrupole experiments. The obtained results show a strong similarity among the spectra, indicating that the internal energy uptake in a MALDI source is comparable with that of 40-eV ions colliding with Ar in a triple-quadrupole instrument.     

<Emphasis Type="Italic">m</Emphasis>-Dissipativity of Some Gradient Systems with Measurable Potential

We consider the operator in L ²(B, ν) and in L ¹(B, ν) with Neumann boundary condition, where U is an unbounded function belonging to for some q ∈(1, ∞), B is the possibly unbounded convex open set in where U is finite and ν(dx) = C exp (−2U (x))dx is a probability measure, infinitesimally invariant for N ₀. We prove that the closure of N ₀ is a m-dissipative operator both in L ²(B, ν) and in L ¹(B, ν). Moreover we study the properties of ergodicity and strong mixing of the measure ν in the L ² case.      

Solvent effects on the adsorption and self-organization of Mn12 on Au(111)

A sulfur-containing single molecule magnet, [Mn12O12(O2CC6H4SCH3)16(H2O)4], was assembled from solution on a Au(111) surface affording both submonolayer and monolayer coverages. The adsorbate morphology and the degree of coverage were inspected by scanning tunneling microscopy (STM), while X-ray photoelectron spectroscopy (XPS) allowed the determination of the chemical nature of the adsorbate on a qualitative and quantitative basis. The properties of the adsorbates were found to be strongly dependent on the solvent used to dissolve the magnetic complex. In particular, systems prepared from tetrahydrofuran solutions gave arrays of isolated and partially ordered clusters on the gold substrate, while samples prepared from dichloromethane exhibited a homogeneous monolayer coverage of the whole Au(111) surface. These findings are relevant to the optimization of magnetic addressing of single molecule magnets on surfaces.     

Anti-angiogenic activity evaluation of secondary metabolites from Calycolpus moritzianus leaves

Angiogenesis is a crucial step in many pathological conditions like cancer, inflammation and metastasis formation; on these basis the search for antiangiogenic agents has widened. In order to identify new compounds able to interfere in the Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1, also known as Flt-1) recognition by VEGFs family members, we screened Calycolpus moritzianus (O. Berg) Burret leaves extracts by a competitive ELISA-based assay. MeOH and CHCl3 extracts and several their fractions demonstrated to be able to prevent VEGF or PlGF interaction with Flt-1, with an inhibition about 50% at concentration of 100 microg/mL. Phytochemical and pharmacological investigation of the active fractions led to the isolation of flavonoids, and terpenes.     

Toxic plants used in ethnoveterinary medicine in Italy

This study was conducted to document the use of toxic or potentially toxic plants for the treatment of ailments in livestock and pets in ethnoveterinary practice in Italy. More than 250 of the entities used (81% for curative purposes) can be toxic unless dosed appropriately. Many (55%) are dietary supplements. The list included 186 species (45%) for internal and 175 (55%) for external use, many used in places where animals are kept. The species belong to 71 families, among which the Fabaceae predominate. The purpose of the study was to provide information that can be validated and associated with correct determination, permitting even potentially dangerous plants to be used in veterinary practice.     

A well-behaved dynamic library of cyclophane formaldehyde acetals incorporating diphenylmethane units

A new well-behaved dynamic library (DL) based on acetal cyclophanes incorporating diphenylmethane units is described. The effective molarities of the first two members of this library of cyclic oligomers C(2) and C(3) have been obtained from concentration profiles. Amplification of the dimer in the presence of a silver template, and cross-equilibration experiments are also reported.     

Rearrangement of aryl- and benzylthiopyridinium imides with participation of a methyl substituent

6-Methyl substituted 2-aryl- and 2-benzylthiopyridinium N-imides reacted with an excess of isocyanates to give N,N-disubstituted exocyclic1H-imidazo[4,5-b]pyridin-2(3H)-ones. The products easily underwent spontaneous [1,5] hydrogen shift to provide the heteroaromatic imidazopyridinone isomers. The transformation implied the initial formation of [1,2,4]triazolo[2,3-a]pyridinium salt, followed by deprotonation and carbamoylation of the methylene moiety, and, finally, a rearrangement following a [1,3] sigmatropic pattern. Mechanistic considerations suggest and some experimental findings reveal the nonconcerted two-step mechanism of the ring transformation step.     

Synthesis and structural characterization of a zinc(II) complex of the mycobactericidal drug isoniazid - Toxicity against Artemia salina

A new zinc(II) complex of the mycobactericidal drug isoniazid (complex 1) was synthesized and characterized by XRD, vibrational spectroscopy (IR, Raman) and thermogravimetric analysis. The complex is constituted by two isoniazid (INH) molecules, six hydration water molecules and two perchlorate counter-ions for each metal center (C₁₂H₂₆N₆Cl₂O₁₆Zn). Zinc(II) adopts a distorted octahedral geometry, where two INH molecules coordinate in a bidentate manner through the hydrazide group (N, O) and the other two isoniazid residues complete the coordination sphere of zinc(II) through their aromatic nitrogen atoms. This coordination pattern gives rise to a 2-D coordination polymer. Complex 1 belongs to the monoclinic system [a = 8.1190(2) Å, b = 17.977(4) Å, c = 9.1051(2) Å and β = 100.87(3)°], space group P2₁. A biological assay with Artemia salina was also performed. Complex 1 is almost 8.5 times more active than the free ligand. Its toxicity against A. salina correlates well with the cytotoxic activity for some human solid tumors. Therefore, antitumoral properties could be expected from complex 1.     

1H, 13C and 15N NMR spectral assignments of adenosine derivatives with different amino substituents at C6-position

The complete (1)H, (13)C and (15)N NMR signals assignment of adenosine derivatives differently substituted at C(6)-position was achieved using one- and two-dimensional experiments (gs-COSY, gs-NOESY, gs-HSQC and gs-HMBC).