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Recoveries of trace pseudoephedrine and methamphetamine residues from impermeable household surfaces: Implications for sampling methods used during remediation of clandestine methamphetamine laboratories

Evaluation of the risk posed by contaminants present during and after decontamination of clandestine methamphetamine laboratories requires a connection between the levels of contaminants measured and those actually present at the scene. The recoveries of pseudoephedrine and methamphetamine from glass, stainless steel, and a range of impermeable surfaces likely to be found in a clandestine laboratory were examined, using GC-MS of derivatized samples as the analytical method. When surfaces had been cleaned prior to drug deposition, wiping with water-dampened filter paper can recover 60-80% of pseudoephedrine immediately after deposition, and at least 50% of the pseudoephedrine still present on a surface after 2 days when deposited at a surface concentration of 2.5 microg/100 cm(2). Wiping with methanol-dampened filter paper could recover 60-90% of the methamphetamine immediately after deposition, and could recover at least 50-60% of the methamphetamine still present after 2 days when 0.6 microg/100 cm(2) was initially deposited on the surface. Recoveries were lower for surfaces that had not been pre-cleaned. Methamphetamine and pseudoephedrine showed significant volatility in both the free base and hydrochloride forms, with experiments in an enclosed format showing up to half the recovered drug being present on a glass plate held about 4mm above a substrate contaminated with one of the drugs at the above surface concentrations after 2 days. It is therefore important to remove any visible bulk contaminants and remove obvious pseudoephedrine or methamphetamine-contaminated surfaces prior to heating, ventilation or sealing of a clandestine laboratory to avoid redistribution of material around the site. A revised method for pseudoephedrine analysis was developed that could also detect the pseudoephedrine-formaldehyde adduct that can form from trace pseudoephedrine present at clandestine laboratories.

Multilayer Nanostructured Porphyrin Arrays Constructed by Layer-by-Layer Self-Assembly

UV-vis absorption, atomic force microscopy (AFM), contact angle, and X-ray reflectivity experiments were performed on thin films deposited on crystalline silicon substrates as alternating layers of a porphyrin with anionic functionality, tetra-5,10,15,20-(4-sulfonatophenyl)porphine (TSPP) or the metalated version, Cu(II)TSPP, and the cationic polyelectrolyte, poly(diallyldimethylammonium chloride) (PDDA). The films were made by dipping in alternating aqueous solutions containing film components (layer-by-layer deposition). Modeling of the X-ray reflectivity data revealed differences in the films' thickness depending on the method of film deposition. An unusual decrease in film thickness after each polyelectrolyte dip was also observed for films using TSSP. UV-vis measurements revealed that a similar amount of TSSP was included within films despite the method of formation. UV-vis measurements also revealed the presence of free-base, H-aggregate, and J-aggregate forms of the porphyrin after TSPP dipping, and the subsequent disappearance of the J-aggregate after dipping in the PDDA solution. A model of film formation was proposed on the basis of the concept of two different types of porphyrin aggregates being present after dipping in porphyrin solution. A layer of porphyrin molecules initially attach to the Si surface such that the planar molecules are arranged side by side as H-aggregates with an excess of J-aggregated material on top. The J-aggregate is then removed and replaced by a layer of PDDA. A change in contact angle of 14 degrees was observed between porphyrin and polyelectrolyte layers due to the more hydrophobic nature of the polymer. The presence of the J-aggregate was confirmed in AFM images obtained from the porphyrin layer. Exposure of the films to solutions of alternating pHs of 10 and 1.8 resulted in reproducible switching of the UV-vis spectra, indicating a possible sensing application.

Role of Salt and Excipient Properties on Disproportionation in the Solid-State

Approximately 50% of active pharmaceutical ingredients (APIs) are manufactured and formulated as salts, due to their enhanced dissolution rates or improved solid state properties. It is essential to maintain the appropriate solid state form of the drug during processing and over the lifetime of the product. The aim of this study was to investigate the contributing factors in the process of disproportionation, whereby the salt converts back to the free form of the drug. Infrared and Raman spectroscopy were used to detect and quantify the formation of free base in physical mixtures with excipients. The pH-solubility relationships were determined based on measured salt solubilities and properties of the free form. The mesylate salts of two model pharmaceutical compounds were found to disproportionate to the free base form when physically mixed with certain common basic excipients and exposed to moderate relative humidities. In contrast, the napsylate salts were much more resistant to disproportionation. The napsylate salts had solubilities more than 3 orders of magnitude lower than the respective mesylate salts, and showed little to no detectable formation of free base. The mesylate salts with higher solubilities showed significant levels of conversion to the free base. It appears that both the solubility and pH(max) (the pH of a solution where there is saturation of both ionized and unionized species) of the salts, as well as the base solubility, play important roles in determining the susceptibility of salts to disproportionate. The extent of conversion was also affected by excipient properties, including basicity, solubility, physical state and surface area.

Folate-conjugated amphiphilic hyperbranched block copolymers based on Boltorn ® H40, poly( l-lactide) and poly(ethylene glycol) for tumor-targeted drug delivery

Folate-conjugated amphiphilic hyperbranched block copolymer (H40–PLA- b-MPEG/PEG–FA) with a dendritic Boltorn ® H40 core, a hydrophobic poly( l-lactide) (PLA) inner shell and a hydrophilic methoxy poly(ethylene glycol) (MPEG) and folate-conjugated poly(ethylene glycol) (PEG–FA) outer shell was synthesized as a carrier for tumor-targeted drug delivery. The block copolymer was characterized using 1H NMR and gel permeation chromatography (GPC) analysis. Due to its core–shell structure, this block polymer forms unimolecular micelles in aqueous solutions. The micellar properties of H40–PLA- b-MPEG/PEG–FA block copolymer were extensively studied by dynamic light scattering (DLS), fluorescence spectroscopy, and transmission electron microscopy (TEM). An anticancer drug, doxorubicin in the free base form (DOX) was encapsulated into H40–PLA- b-MPEG/PEG–FA micelles. The DOX-loaded micelles provided an initial burst release (up to 4 h) followed by a sustained release of the entrapped DOX over a period of about 40 h. Cellular uptake of the DOX-loaded H40–PLA- b-MPEG/PEG–FA micelles was found to be higher than that of the DOX-loaded H40–PLA- b-MPEG micelles because of the folate-receptor-mediated endocytosis, thereby providing higher cytotoxicity against the 4T1 mouse mammary carcinoma cell line. In vitro degradation studies revealed that the H40–PLA- b-MPEG/PEG–FA block copolymer hydrolytically degraded into polymer fragments within six weeks. These results indicated that the micelles prepared from the H40–PLA- b-MPEG/PEG–FA block copolymer have great potential as tumor-targeted drug delivery nanocarriers.

Can phthalocyanines and their substituted α-para-(methoxy)phenyl derivatives act as photosensitizers in photodynamic therapy? A TD-DFT study

A time-dependent density functional theory study (TD-DFT) is presented regarding the substituent effects on the Q-bands of two classes of non-planar phthalocyanines: the alpha-octaphenyl and p-alpha-octamethoxyphenyl substituted compounds, in their free-base and zinc complex forms. Singlet vertical excitation energies, computed at the PBE0/SVP//BP86/SVP level of theory also including bulk solvent effects (COSMO model), resulted within 0.1 eV of experiment. The experimental red-shift for the Q-band, going from the phenylated to the methoxyphenylated case, was well-reproduced theoretically and in the latter case it was found to depend mainly on the nature of the substituents and partly on structure distortion effects. The energetic gap between the singlet ground and first triplet excited state was calculated in solvent to be 1.28 eV for the free-base phthalocyanine (H2Pc) and 1.45 eV for the unsubstituted zinc complex (ZnPc) and lower than 0.98 eV for all the other compounds, which is the energetic lower limit for a molecule to act as photosensitiser in photodynamic therapy according to a Type II reaction mechanism. As a consequence, since this property-requirement for drugs used in photodynamic therapy is not fulfilled by the investigated near-infrared photosensitizers, they cannot be proposed as candidates for their use in this medical treatment.

The dynamics of sorption of sulfuric acid by weakly basic polyacrylic anion exchangers

The nonequilibrium dynamics of sorption of sulfuric acid by free base forms of Amberlite IRA-67 and Lewatite VP.OC.1072 weakly basic anion exchangers is studied. It is established that, in hydrodynamic regimes of filtration, which are typical of OH filters of the first stage of water-desalting plants, the limiting stage of sorption kinetics is inside diffusion. It is concluded that the process is correctly described by an asymptotic solution to the inside-diffusion model of sorption dynamics.

Evolution of stimulants to treat ADHD: transdermal methylphenidate

The following comprehensive review describes the evolution of stimulant drug formulations used in the treatment of attention-deficit/hyperactivity disorder (ADHD). Emphasis is placed on the basic and clinical pharmacology of the dl-methylphenidate (MPH) transdermal system (MTS). The pharmacokinetic and pharmacodynamic literature pertaining to MPH and amphetamine enantiomers was reviewed in the context of ADHD therapy and MTS as a treatment option. MTS incorporates MPH into an adhesive monolithic matrix, using the free base form of the drug to facilitate transdermal absorption. MTS technology minimizes contact dermatitis by eliminating to need for percutaneous penetration enhancers. After a lag time of approximately 2 h, plasma concentrations of the therapeutic d-MPH isomer become detectable, then continuously rise over the course of the recommended 9 h wear time. Concentrations of l-MPH typically attain 40-50% that of d-MPH (vs. 1-2% following oral MPH). Unauthorized MTS removal poses some misuse liability and over 50% of MTS drug content remains in the discarded system. While liquid or chewable MPH formulations overcome potential swallowing difficulties, as do sprinkled once-daily extended-release (ER) MPH products, only MTS addresses swallowing difficulties while also offering a flexible individualized MPH exposure time in a once-daily MPH regimen.

Self-Assembly of Lyotropic Chromonic Liquid Crystal Sunset Yellow and Effects of Ionic Additives

Lyotropic chromonic liquid crystals (LCLCs) are formed by molecules with ionic groups at the periphery that associate into stacks through noncovalent self-assembly while in water. The very existence of the nematic (N) phase in the typical LCLC, the dye Sunset Yellow (SSY) is a puzzle, as the correlation length associated with the stacking, as measured in the X-ray experiments, is too short to explain the orientational order by the Onsager model. We propose that the aggregates can be more complex than simple rods and contain "stacking faults" such as junctions with a shift of neighboring molecules, 3-fold junctions, etc. We study how ionic additives, such as salts of different valency and pH-altering agents, alter the N phase of SSY purified by recrystallization. The additives induce two general trends: (a) stabilization of the N phase, caused by the mono and divalent salts (such as NaCl), and evidenced by the increase of the N-to-I transition temperature and the correlation length; (b) suppression of the N phase manifested in the decrease of the N-to-I transition temperature and in separation of the N phase into a more densely packed N phase or the columnar (C) phase, coexisting with a less condensed I phase. The scenario (b) can be triggered by simply increasing pH (adding NaOH). The effects produced by tetravalent spermine fall mostly into the category (b), but the detail depends on whether this additive is in its salt form or a free base form. The base form causes changes through changes in pH and possible excluded volume effects whereas the salt form might disrupt the structure of SSY aggregates.

Pellet characteristics and drug release when the form of propranolol is fixed as moles or mass in formulations for extruded and spheronized Carbopol-containing pellets

Characteristics of Carbopol-containing pellets have been shown to be dependent on the form of the weakly basic drug, propranolol, when the drug forms are fixed as masses in the formulations. To further investigate the effect of the drug forms on pellet and drug release characteristics, the drug forms were incorporated as a fixed number of moles in the formulation. Forms of propranolol, viz. the free base and the hydrochloride and maleate salt forms, resulted in different yield, roundness, smoothness, and friability, but the average pellet diameter was not affected. The free base form was released more slowly than the other two forms. Mathematical analysis of the release data revealed that Fickian diffusion and polymer relaxation contributed to the release mechanism in each case, although polymer relaxation was more influential with the free base form.

Asymmetric aza-Michael reactions of alpha,beta-unsaturated ketones with bifunctional organic catalysts.

Asymmetric aza-Michael reactions of alpha,beta-unsaturated ketones with bifunctional organic catalysts.

Identification of a free base form Manzamine A from a marine sponge, Acanthostrongylophora aff. ingens (Thiele, 1899), and its neuritogenic activity

Two manzamine-class alkaloids, manzamine A (1) and 8-hydroxymanzamine (2) were isolated from a Japanese marine sponge Acanthostrongylophora aff. Ingens, together with three known alkaloids manzamine E (3), manzamine F (4), and manzamine X (5). The spectral features of 1 and 2 were different from the reported data [1,2]. Detailed structure analysis using 2D NMR revealed the structure of 1 and 2 as a free base form of hydrochloric salt (6, 7). These manzamine-class alkaloids showed neuritogenic activity against Neuro 2a cells.

Propranolol forms affect properties of Carbopol-containing extruded-spheronized beads

Drug release rates from extruded-spheronized beads containing Carbopol have been shown to be dependent on the chemical nature of different types of drugs. To further clarify solubility, salt counterion, pH, and ionic strength effects on Carbopol bead characteristics, including but not limited to the drug release profile, the present study utilizes propranolol in its free base, hydrochloride, and maleate forms. Different forms of propranolol resulted in different bead average diameter, roundness, and smoothness, but the ruggedness was not affected. Release profiles for the two salt forms were nearly superimposable, but the free base form was released more slowly. Mathematical analysis of the release data revealed that Fickian diffusion and polymer relaxation were contributing factors to the release mechanism in each case, although polymer relaxation was more influential with the free base form. In light of these results, the choice of the form of a drug should be considered carefully when preparing Carbopol-containing beads produced by extrusion-spheronization.

Chemical precipitation of copper from copper–zinc solutions onto selective sorbents

The selective sorption and multiple concentration of copper in the form of an ultradisperse precipitate from a diluted Cu 2+–Zn 2+-solution has been investigated. The selective sorption is accomplished by means of weakly basic anion exchangers in their free base forms. Regeneration of the sorbent and conversion of Cu 2+ to Cu 0 is carried out by means of a chemical reduction in the resin phase. Thus the resins can be reused for sorption of further copper ions. The process has been investigated in both, batch and packed bed experiments. After multiple saturation–reduction cycles an accumulation of metallic copper on the surface and in the pores of the sorbent is observed. The presence of finely dispersed metallic copper leads to the additional sorption of the Cu 2+ ions due to a synproportional reduction–oxidation reaction. The total uptake of copper after several cycles amounts to more than 300 % of the anion exchange capacity.

Porphyrins as SERRS spectral probes of chemically functionalized Ag nanoparticles

The results of surface-enhanced resonance Raman scattering (SERRS) spectral probing of citrate- and/or citric acid-modified Ag nanoparticles by selected free-base porphyrins, namely a tetracationic 5,10,15,20-tetrakis(1-methyl-4-pyridiniumyl)porphine and neutral 5,10,15,20-tetra(pyridyl)porphine (H 2TPyP) and 5,10,15,20-tetrakis(4-aminophenyl)porphine (H 2TAPP) are reported, along with a novel procedure of the functionalized Ag nanoparticle hydrosols preparation by laser ablation of a Ag target in aqueous sodium citrate and/or citric acid solutions of various concentrations. SERRS spectra obtained from the Ag nanoparticle hydrosol/porphyrin system were analyzed using the spectral marker bands of free-base, Ag metallated and diacid forms. In freshly prepared SERRS-active systems, adsorbed citrate was found to function as an efficient molecular spacer for positively charged porphyrin species both in the pH-neutral and in the acidic media, allowing for SERRS spectral detection of not only cationic, but also additionally protonized neutral porphyrins in the native free-base (and/or, at low pH, in the diacid) form without denaturation by Ag incorporation. Furthermore, a substantial increase of the SERRS signal observed for H 2TPyP and H 2TAPP in systems with Ag nanoparticles prepared by laser ablation in 1 × 10 −2 M citric acid solutions is attributed to both the electromagnetic enhancement increase stemming from the presence of hot spots in compact aggregates of touching and intergrown Ag nanoparticles (visualized by /HR/-TEM), and from the molecular resonance enhancement increase originating from a close match between the Soret band of the diacid form (440 nm) and the 457.9 nm excitation. For H 2TAPP, the large SERRS enhancement manifests itself in the 1 × 10 −10 M SERRS spectral detection limit.

Supramolecular Reactivity of Porphyrins with Mixed Iodophenyl and Pyridyl meso-Substituents

This study evaluates the supramolecular reactivity of the 5-(4′-pyridyl)-10,15,20-tris(4′-iodophenyl)porphyrin (PyTIPP) and 5,15-bis(4′-pyridyl)-10,20-bis(4′-iodophenyl)porphyrin (PyDIPP) platforms in their free base and metalated forms, utilizing metal–ligand coordination and halogen bond synthons in the construction of polymeric as well as oligomeric assemblies. Free base PyTIPP and PyDIPP moieties form extended supramolecular layers held together by intermolecular N···I and I···π interactions, which π···π stack in an offset manner to yield layered crystals. The metalated monopyridyl derivative Co-PyTIPP (as well as its Zn-PyTIPP analogue) assembles into cyclic tetrameric supermolecule via coordination of the pyridyl function of one species to the core metal ion of an adjacent unit. On the other hand, the bis-pyridyl Zn-PyDIPP scaffold constructs a robust framework solid of extended honeycomb architecture by polymeric self-coordination. These findings provide useful protocols for rational design of the different modes of supramolecular porphyrin ensembles, which are valid in reaction media lacking polar reagents with competing affinity for the functional groups of the porphyrin units. In the latter context, PyDIPP in the presence of benzoic acid forms discrete solvated entities, where the pyridyl N-sites engage in hydrogen bonds to the carboxylic acids, preventing direct inter-porphyrin association.

On the mechanism of drug release from oil suspensions in vitro using local anesthetics as model drug compounds

The objective of this study was to gain insight into factors influencing the drug release kinetics from oil suspensions. The in vitro drug release from suspensions was investigated at pH 7.4 using the local anesthetics, bupivacaine and ropivacaine, as model drug compounds. Two dialysis membrane-based in vitro release models differing with respect to stirring of the donor compartment were employed to study the release characteristics of oil suspensions comprising the free base or the corresponding drug hydrochloride salt. In the rotating dialysis cell model identical release profiles from aqueous and oil suspensions of the base form were obtained for both ropivacaine and bupivacaine. From the steady state fluxes, drug concentrations in the aqueous donor compartment were found to be in agreement with drug solubilities at pH 7.4. Also relatively fast transformation of a sesame oil suspension of the oil insoluble ropivacaine hydrochloride salt into an aqueous suspension of ropivacaine base was observed. Collectively, these observations indicate a lability of the oil film surrounding the solid particles eventually caused by rotation of the donor cell. In the Float A Lyzer ® model, which operates at much less intensive stirring, significantly slower release rates from aqueous and oil suspensions of ropivacaine base were obtained. In the latter model, ropivacaine was released faster from oil suspensions containing the hydrochloride salt than from the corresponding oil suspensions of the free base form. These findings suggest that the oil film surrounding the particles also is instable in the absence of significant shear forces.

Control of the Orbital Delocalization and Implications for Molecular Rectification in the Radical Anions of Porphyrins with Coplanar 90° and 180° β,β‘-Fused Extensions

Through-porphyrin electronic communication is investigated using "linear-type" and "corner-type" bis(quinoxalino)porphyrins in free-base form and their ZnII, CuII, NiII, and PdII derivatives. These compounds are porphyrins with quinoxalines fused on opposite or adjacent beta,beta'-pyrrolic positions; they were synthesized from 5,10,15,20-tetrakis(3,5-di-tert-butylphenyl)-porphyrin-2,3,12,13- and -2,3,7,8-tetraone, respectively, by reaction with 1,2-phenylenediamine. The degree of electron spin delocalization into the fused rings in the pi-radical anions of the free-base and metal(II) bisquinoxalinoporphyrins was elucidated by electrochemistry, UV-vis absorption, and electron spin resonance (ESR) spectra of the singly reduced species and density functional theory calculations. Hyperfine splitting patterns in the ESR spectra of the pi-radical anions show that symmetric molecules have delocalized electron spin, indicating that significant inter-quinoxaline interactions are mediated through the central porphyrin unit, these interactions being sufficient to guarantee through-molecule conduction. However, when molecular symmetry is broken by tautomeric exchange of the inner nitrogen hydrogens in the free-base porphyrin with a corner-type quinoxaline substitution pattern, the pi-radical anion becomes confined so that one quinoxaline group is omitted from spin delocalization. This indicates the appearance of a unidirectional barrier to through-molecule conduction, suggesting a new motif for chemically controlled rectification.

Neuritogenic Activity-Guided Isolation of a Free Base Form Manzamine A from a Marine Sponge, Acanthostrongylophora aff. ingens (Thiele, 1899)

Two manzamine-class alkaloids, manzamine A (1) and 8-hydroxymanzamine (2) were isolated from a Japanese marine sponge Acanthostrongylophora aff. ingens, together with three known alkaloids manzamine E (3), manzamine F (4), and manzamine X (5). The spectral features of 1 and 2 were different from the reported data. Detailed structure analysis using 2D NMR revealed the structure of 1 and 2 as a free base form of hydrochloric salt. These manzamine-class alkaloids showed neuritogenic activity against Neuro 2a cells.

The equilibrium sorption of sulfuric acid by weakly basic polyacrylic anion exchangers synthesized on the basis of polyamines

The equilibrium ion-exchange sorption of sulfuric acid by the free base form of weakly basic polyacrylic anion exchangers with the gel (Relite MG1) and porous (Relite MG1/P) structures was studied. It was proved that the bisulfate variety of the anion exchangers did not form. Solutions of resinates were found to be nonideal. Their nonideality was analyzed in terms of the theory of exchange equilibria to suggest a model of the exchange of doubly-charged anions on fixed polyamine exchange centers of Relite MG1 and Relite MG1/P anion exchangers. The type of the ion was found to have no effect on sorption parameters.

Two-photon absorption cross-sections and time-resolved fluorescence imaging using porphyrin photosensitisers

Three porphyrin systems have been characterised for use in two-photon fluorescence imaging of biological samples. We have determined the two-photon absorption cross sections (sigma(2)) of the di-cation, free-base and metallated forms of hematoporphyrin derivative (HpD), hematoporphyrin IX (Hp9) and a boronated protoporphyrin (BOPP) using the open-aperture Z-scan and the two-photon induced fluorescence (TPIF) techniques at an excitation wavelength of 800 nm. The insertion of either protons or a metal ion into the macrocycle is shown not to significantly influence the sigma(2) of the porphyrins. Two-photon time-resolved fluorescence images of C6 glioma cells transfected with a free-base form of the BOPP have been obtained as a function of the porphyrin concentration. These studies reveal a maximum useful porphyrin concentration for fluorescence imaging purposes of approximately 30 microg mL(-1).