Confirmation of sulfamethazine, sulfathiazole, and sulfadimethoxine residues in condensed milk and soft-cheese products by liquid chromatography/tandem mass spectrometry

A liquid chromatography/tandem mass spectrometry method (LC/MS/MS) is described for the simultaneous detection of 3 sulfonamide drug residues at 1.25 ppb in condensed milk and soft-cheese products. The 3 sulfonamide drugs of interest are sulfathiazole (STZ), sulfamethazine (SMZ), and sulfadimethoxine (SDM). The method includes extraction of the product with phosphate buffer, centrifugation of the diluted product, and application of a portion of the extract onto a polymeric solid-phase extraction cartridge. The cartridge is washed with water, and the sulfonamides are eluted with methanol. After evaporation, the residue is dissolved in 0.1% formic acid solution, and the solution is filtered before analysis by LC/MS/MS. The LC/MS/MS program involved a series of time-scheduled selected-reaction monitoring transitions. The transitions of MH+ to the common product ions at m/z 156, 108, and 92 were monitored for each residue. In addition, SMZ and SDM had a fourth significant and unique product ion transition that could be measured. Validation was performed with control and fortified-control condensed bovine milk with 2.5, 5, and 10 ppb sulfonamides. This method was applied to imported flavored and unflavored condensed milk and cream cheese bars. The presence of STZ and SMZ residues was confirmed in 3 out of 6 products.     

Picosecond dynamics of nonthermalized excited states in tris(2,2-bipyridine)ruthenium(II) derivatives elucidated by high energy excitation

The picosecond excited-state dynamics of several derivatives have been investigated using high photon energy excitation combined with picosecond luminescence detection. Instrument response-limited fluorescence (tau(1) approximately equal to 3-5 ps) at 500 nm was observed for all of the complexes, while longer-lived emission (tau(2) > 50 ps), similar in energy, was observed for only some of the complexes. Interestingly, the presence of tau(2) required substitution at the 4,4-positions of the bipyridine ligands and D(3) symmetry for the complex; only the 4,4-substituted homoleptic complexes exhibited tau(2). On the basis of previous assignments of the ultrafast dynamics measured for Ru(bpy)(2+)3 and Ru(dmb)(2+)3, tau(2) has been tentatively ascribed to relaxation from higher electronic or vibrational levels in the triplet manifold having slightly more triplet character than the state responsible for tau(1). However, given that the kinetics for these transition metal complexes are highly dependent on both pump and probe wavelengths and that there is considerable interest in utilizing such complexes for electron transfer in the nonergodic limit, further characterization of the state giving rise to tau(2) is warranted.     

Conformational control of excited-state dynamics in highly distorted Ru(II) polypyridyl complexes

Tris(bipyridyl)ruthenium(II) complexes modified such that one of the bipyridines is appended with a crown ether display luminescence that is responsive to complexation with metal ions. The parent species, Ru(bpy)3(2+), is moderately luminescent, with an emission lifetime of about 1 micros in fluid solution at room temperature. The modified complexes are much less emissive, with lifetimes near 1 ns. Conformational flexibility and distortion in the crown-ether complexes enhance nonradiative decay. Noncovalent binding of metal ions, however, restores luminescence intensity by reducing nonradiative decay and increasing the lifetime 10- to 100-fold. Reported here are the syntheses and steady-state and time-resolved luminescence measurements in addition to other supporting spectroscopic characterization. Seven metals were investigated; significant luminescence enhancements occur in the presence of Mg2+, Ca2+, and Pb2+. Effective concentrations of metal ions range from tens of microM to hundreds of mM. The steady-state enhancements are readily measured, but they are less than would be expected from the lifetime changes, partly because only a portion (not more than 50%) of the fast (1 ns) decay in Ru(bpy)2(bpy-crown) is capable of converting to the conformation possessing the longer lifetime. A photophysical model is proposed to explain these and other observations.     

Dark-field scanning in situ spectroscopy platform for broadband imaging of resected tissue

A dark-field geometry spectral imaging system is presented to raster scan thick tissue samples in situ in 1.5 cm square sections, recovering full spectra from each 100 μm diameter pixel. This spot size provides adequate resolution for wide field scanning, while also facilitating scatter imaging without requiring sophisticated light-tissue transport modeling. The system is demonstrated showing accurate estimation of localized scatter parameters and the potential to recover absorption-based contrast from broadband reflectance data measured from 480 nm up to 750 nm in tissue phantoms. Results obtained from xenograft pancreas tumors show the ability to quantitatively image changes in localized scatter response in this fast-imaging geometry. The polychromatic raster scan design allows the rapid scanning necessary for use in surgical/clinical applications where timely decisions are required about tissue pathology.     

Intracellular Photophysics of an Osmium Complex bearing an Oligothiophene Extended Ligand

This contribution describes the excited-state properties of an Osmium-complex when taken up into human cells. The complex 1 [Os(bpy)₂(IP-4T)](PF₆)₂ with bpy=2,2′-bipyridine and IP-4T=2-{5′-[3′,4′-diethyl-(2,2′-bithien-5-yl)]-3,4-diethyl-2,2′-bithiophene}imidazo[4,5-f][1,10]phenanthroline) can be discussed as a candidate for photodynamic therapy in the biological red/NIR window. The complex is taken up by MCF7 cells and localizes rather homogeneously within in the cytoplasm. To detail the sub-ns photophysics of 1 , comparative transient absorption measurements were carried out in different solvents to derive a model of the photoinduced processes. Key to rationalize the excited-state relaxation is a long-lived ³ILCT state associated with the oligothiophene chain. This model was then tested with the complex internalized into MCF7 cells, since the intracellular environment has long been suspected to take big influence on the excited state properties. In our study of 1 in cells, we were able to show that, though the overall model remained the same, the excited-state dynamics are affected strongly by the intracellular environment. Our study represents the first in depth correlation towards ex-vivo and in vivo ultrafast spectroscopy for a possible photodrug.     

Tumor vascular area correlates with photosensitizer uptake: analysis of verteporfin microvascular delivery in the Dunning rat prostate tumor

The parameters that limit supply of photosensitizer to the cancer cells in a solid tumor were systematically analyzed with the use of microvascular transport modeling and histology data from frozen sections. In particular, the vascular permeability transport coefficient and the effective interstitial diffusion coefficient were quantified for Verteporfin-for-Injection delivery of benzoporphyrin derivative (BPD). Orthotopic tumors had higher permeability and diffusion coefficients (Pd = 0.036 microm/s and D = 1.6 microm(2)/s, respectively) as compared to subcutaneously grown tumors (Pd = 0.025 microm/s and D = 0.9 microm2/s, respectively), likely due to the fact that the vessel patterns are more homogeneous orthotopically. In general, large intersubject and intratumor variability exist in the verteporfin concentration, in the range of 25% in plasma concentration and in the range of 20% for tissue concentrations, predominantly due to these microregional variations in transport. However, the average individual uptake of photosensitizer in tumor tissue was only correlated to the total vascular area within the tumor (R2 = 64.1%, P < 0.001). The data are consistent with a view that microregional variation in the vascular permeability and interstitial diffusion rate contribute the spatial heterogeneity observed in verteporfin uptake, but that average supply to the tissue is limited by the total area of perfused blood vessels. This study presents a method to systematically analyze micro-heterogeneity as well as possible methods to increase delivery and homogeneity of photosensitizer within tumor tissue.