Methamphetamine Removal from Aquatic Environments by Magnetic Microrobots with Cyclodextrin Chiral Recognition Elements.

The growing consumption of drugs of abuse together with the inefficiency of the current wastewater treatment plants toward their presence has resulted in an emergent class of pollutants. Thus, the development of alternative approaches to remediate this environmental threat is urgently needed. Microrobots, combining autonomous motion with great tunability for the development of specific tasks, have turned into promising candidates to take on the challenge. Here, hybrid urchin-like hematite (α-Fe2O3) microparticles carrying magnetite (Fe3O4) nanoparticles and surface functionalization with organic ß-cyclodextrin (CD) molecules are prepared with the aim of on-the-fly encapsulation of illicit drugs into the linked CD cavities of moving microrobots. The resulting mag-CD microrobots are tested against methamphetamine (MA), proving their ability for the removal of this psychoactive substance. A dramatically enhanced capture of MA from water with active magnetically powered microrobots when compared with static passive CD-modified particles is demonstrated. This work shows the advantages of enhanced mass transfer provided by the externally controlled magnetic navigation in microrobots that together with the versatility of their design is an efficient strategy to clean polluted waters.

Understanding methiopropamine, a new psychoactive substance: an in-depth review on its chemistry, pharmacology and implications to human health.

Methiopropamine or 1-(thiophen-2-yl)-2-methylaminopropane (MPA) is a thiophene ring-based structural analogue of methamphetamine, first synthesized in 1942 but become popular when it started to be available for purchase on websites selling 'legal highs' since 2010. While it is legally controlled in many countries, it remains readily accessible and frequently encountered in recreational settings. The growing prevalence of MPA use results in new therapeutic challenges. Relatively few studies have focused on its pharmacodynamics and pharmacokinetics, making it important to better understand its potential risks and harmful effects in humans in terms of its toxicity. This review provides a comprehensive profiling of MPA toxicological properties, including its chemical properties, analytical methods, prevalence, patterns of use, and legal status. Additionally, it discusses the drug's effects on the central nervous system, its potential for addiction, and its adverse physical and mental health effects. Improving the understanding of safety aspects of MPA and how it imposes health threats for public health will guide the development of therapeutic approach of its intoxication and guide the authorities in deciding its legal status.

Label-free profiling of DNA aptamer-small molecule binding using T5 exonuclease.

In vitro aptamer isolation methods can yield hundreds of potential candidates, but selecting the optimal aptamer for a given application is challenging and laborious. Existing aptamer characterization methods either entail low-throughput analysis with sophisticated instrumentation, or offer the potential for higher throughput at the cost of providing a relatively increased risk of false-positive or -negative results. Here, we describe a novel method for accurately and sensitively evaluating the binding between DNA aptamers and small-molecule ligands in a high-throughput format without any aptamer engineering or labeling requirements. This approach is based on our new finding that ligand binding inhibits aptamer digestion by T5 exonuclease, where the extent of this inhibition correlates closely with the strength of aptamer-ligand binding. Our assay enables accurate and efficient screening of the ligand-binding profiles of individual aptamers, as well as the identification of the best target binders from a batch of aptamer candidates, independent of the ligands in question or the aptamer sequence and structure. We demonstrate the general applicability of this assay with a total of 106 aptamer-ligand pairs and validate these results with a gold-standard method. We expect that our assay can be readily expanded to characterize small-molecule-binding aptamers in an automated, high-throughput fashion.

High Coverage Profiling of Carboxylated Metabolites in HepG2 Cells Using Secondary Amine-Assisted Ultrahigh-Performance Liquid Chromatography Coupled to High-Resolution Mass Spectrometry.

Carboxylic metabolites are an important class of metabolites, which widely exist in mammals with various types. Chemical isotope labeling liquid chromatography-mass spectrometry (CIL-LC-MS) has been widely used for the detection of carboxylated metabolites. However, high coverage analysis of carboxylated metabolites in biological samples is still challenging due to improper reactivity and selectivity of labeling reagents to carboxylated metabolites. In this study, we used N-methylphenylethylamine (MPEA) to label various types of carboxylated metabolites including short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs), long-chain fatty acids (LCFAs), polycarboxylic acids (polyCAs), amino acids (AAs), and aromatic acids. Additionally, metabolites containing other functional groups, such as phenol, sulfhydryl, and phosphate groups, could not be labeled under the conditions of MPEA labeling. After MPEA labeling, the detection sensitivity of carboxylic acids was increased by 1-2 orders of magnitude, and their chromatographic retention on a reversed-phase (RP) column was enhanced (RT > 3 min). Under optimized labeling conditions, we used MPEA and d3-N-methylphenylethylamine (d3-MPEA) for high coverage screening of carboxylated metabolites in HepG2 cells by ultrahigh-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS). As a result, a total of 403 potential carboxylated metabolites were obtained of which 68 were confirmed based on our established in-house chemically labeled metabolite database (CLMD). SCFAs, MCFAs, LCFAs, polyCAs, AAs, and aromatic acids were all detected in HepG2 cell extracts. Due to the successful identification of AAs, the current method increased the coverage of carboxylated metabolites compared with our previous work. Moreover, 133 and 109 carboxylated metabolites with changed contents were obtained in HepG2 cells incubated with curcumin and R-3-hydroxybutyric acid, respectively. In general, our established method realized high coverage analysis of carboxylated metabolites in HepG2 cells.

S-(+)-Pentedrone and R-(+)-methylone as the most oxidative and cytotoxic enantiomers to dopaminergic SH-SY5Y cells: Role of MRP1 and P-gp in cathinones enantioselectivity.

Cathinone derivatives are the most representative group within new drugs market, which have been described as neurotoxic. Since cathinones, as pentedrone and methylone, are available as racemates, it is our aim to study the neuronal cytotoxicity induced by each enantiomer. Therefore, a dopaminergic SH-SY5Y cell line was used to evaluate the hypothesis of enantioselectivity of pentedrone and methylone enantiomers on cytotoxicity, oxidative stress, and membrane efflux transport (confirmed by in silico studies). Our study demonstrated enantioselectivity of these cathinones, being the S-(+)-pentedrone and R-(+)-methylone the most oxidative enantiomers and also the most cytotoxic, suggesting the oxidative stress as main cytotoxic mechanism, as previously described in in vitro studies. Additionally, the efflux transporter multidrug resistance associated protein 1 (MRP1) seems to play, together with GSH, a selective protective role against the cytotoxicity induced by R-(-)-pentedrone enantiomer. It was also observed an enantioselectivity in the binding to P-glycoprotein (P-gp), another efflux protein, being the R-(-)-pentedrone and S-(-)-methylone the most transported enantiomeric compounds. These results were confirmed, in silico, by docking studies, revealing that R-(-)-pentedrone is the enantiomer with highest affinity to MRP1 and S-(-)-methylone and R-(-)-pentedrone are the enantiomers with highest affinity to P-gp. In conclusion, our data demonstrated that pentedrone and methylone present enantioselectivity in their cytotoxicity, which seems to involve different oxidative reactivity as well as different affinity to the P-gp and MRP1 that together with GSH play a protective role.

Polyoxometalate-Based Frameworks as Adsorbents for Drug of Abuse Extraction from Hair Samples.

The linkage of molecular components into functional heterogeneous framework materials has revolutionized modern materials chemistry. Here, we use this principle to design polyoxometalate-based frameworks as high affinity adsorbents for drugs of abuse, leading to their application in solid-phase extraction analysis. The frameworks are assembled by the reaction of a Keggin-type polyanion, [SiW12O40]4-, with lanthanoids Dy(III), La(III), Nd(III), and Sm(III) and the multidentate linking ligand 1,10-phenanthroline-2,9-dicarboxylic acid (H2PDA). Their reaction leads to the formation of crystalline 1D coordination polymers. Because of the charge mismatch between the lanthanoids (+3) and the dodecasilicotungstate (-4), we observe incorporation of the PDA2- ligands into crystalline materials, leading to four polyoxometalate-based frameworks where Keggin-type heteropolyanions are linked by cationic {Lnn(PDA)n} groups (Ln = Dy (1), La (2), Nd (3), and Sm (4)). Structural analysis of the polyoxometalate-based frameworks suggested that they might be suitable for surface binding of common drugs of abuse via supramolecular interactions. To this end, they were used for the extraction and quantitative determination of four model drugs of abuse (amphetamine, methamphetamine, codeine, and morphine) by using micro-solid-phase extraction (D-µSPE) and high-performance liquid chromatography (HPLC). The method showed wide linear ranges, low limits of detection (0.1-0.3 ng mL-1), high precision, and satisfactory spiked recoveries. Our results demonstrate that polyoxometalate-based frameworks are suitable sorbents in D-µSPE for molecules containing amine functionalities. The modular design of these networks could in the future be used to expand and tune their substrate binding behavior.

Neurotransmitter and psychostimulant recognition by the dopamine transporter.

Na(+)/Cl(-)-coupled biogenic amine transporters are the primary targets of therapeutic and abused drugs, ranging from antidepressants to the psychostimulants cocaine and amphetamines, and to their cognate substrates. Here we determine X-ray crystal structures of the Drosophila melanogaster dopamine transporter (dDAT) bound to its substrate dopamine, a substrate analogue 3,4-dichlorophenethylamine, the psychostimulants d-amphetamine and methamphetamine, or to cocaine and cocaine analogues. All ligands bind to the central binding site, located approximately halfway across the membrane bilayer, in close proximity to bound sodium and chloride ions. The central binding site recognizes three chemically distinct classes of ligands via conformational changes that accommodate varying sizes and shapes, thus illustrating molecular principles that distinguish substrates from inhibitors in biogenic amine transporters.

Fluorescence resonance energy transfer-thermal lens spectrometry (FRET-TLS) as molecular counting of methamphetamine.

A novel and sensitive approach has been presented for the determination of methamphetamine (METH) based on fluorescence resonance energy transfer-thermal lens spectrometry (FRET-TLS). Due to the affinity of fluorescein molecules to the surface of AuNPs through the electrostatic interaction and thereby caused reduction of the distance between fluorescein and AuNPs, the best way for de-excitation of excited fluorescein is FRET. The energy absorbed by fluorescein transferred to AuNPs causes enhancement of the thermal lens effect. The thermal lens of the fluorescence molecule could be enhanced through a proper acceptor. Upon the addition of methamphetamine, the fluorescein molecules are detached from the surface of AuNPs, due to the stronger adsorption of methamphetamine. As a result, the fluorescence of fluorescein recovered, and the thermal lens effect of fluorescein decreased. The mechanism of energy transfer was evaluated by two different methods including time-resolved spectroscopy and thermal lens spectrometry. Under the optimal conditions, the thermal lens signal was linearly proportional to methamphetamine concentration in the range 5 - 80 nM. The limit of detection and limit of quantitation were 1.5 nM and 4.5 nM, respectively. The detection volume and limit of molecules in the detection volume were 960 attoliter and 87 molecules, respectively. The method was successfully applied for the determination of methamphetamine in human blood plasma and urine.

Pseudoephedrine-Benefits and Risks.

Pseudoephedrine (PSE) is a drug with a long history of medical use; it is helpful in treating symptoms of the common cold and flu, sinusitis, asthma, and bronchitis. Due to its central nervous system (CNS) stimulant properties and structural similarity to amphetamine, it is also used for non-medical purposes. The substance is taken as an appetite reducer, an agent which eliminates drowsiness and fatigue, to improve concentration and as a doping agent. Due to its easier availability, it is sometimes used as a substitute for amphetamine or methamphetamine. Pseudoephedrine is also a substrate (precursor) used in the production of these drugs. Time will tell whether legal restrictions on the sale of this drug will reduce the scale of the problem associated with its misuse.

DFT-D4 Insight into the Inclusion of Amphetamine and Methamphetamine in Cucurbit[7]uril: Energetic, Structural and Biosensing Properties.

The host-guest interactions of cucurbit[7]uril (CB[7]) as host and amphetamine (AMP), methamphetamine (MET) and their enantiomeric forms (S-form and R-form) as guests were computationally investigated using density functional theory calculations with the recent D4 atomic-charge dependent dispersion corrections. The analysis of energetic, structural and electronic properties with the aid of frontier molecular orbital analysis, charge decomposition analysis (CDA), extended charge decomposition analysis (ECDA) and independent gradient model (IGM) approach allowed to characterize the host-guest interactions in the studied systems. Energetic results indicate the formation of stable non-covalent complexes where R-AMP@CB[7] and S-AMP@CB[7] are more stable thermodynamically than R-MET@CB[7] and S-MET@CB[7] in gas phase while the reverse is true in water solvent. Based on structural analysis, a recognition mechanism is proposed, which suggests that the synergistic effect of van der Waals forces, ion-dipole interactions, intermolecular charge transfer interactions and intermolecular hydrogen bonding is responsible for the stabilization of the complexes. The geometries of the complexes obtained theoretically are in good agreement with the X-ray experimental structures and indicate that the phenyl ring of amphetamine and methamphetamine is deeply buried into the cavity of CB[7] through hydrophobic interactions while the ammonium group remains outside the cavity to establish hydrogen bonds with the portal oxygen atoms of CB[7].

Enantioselectivity on the absorption of methylone and pentedrone using Caco-2 cell line: Development and validation of an UHPLC method for cathinones quantification.

Synthetic cathinones, such as methylone and pentedrone, are psychoactive derivatives of cathinone, sold in the internet as "plant food" or "bath salts". However, the level at which these compounds and their enantiomers cross the intestinal barrier has not been yet determined. Thus, the present study aimed to analyze the enantioselectivity on the permeability of these drugs through the intestinal barrier by using the Caco-2 cell line, a widely used in vitro model for drug permeability studies. To achieve this goal, an UHPLC-UV method was developed and validated to quantify both synthetic cathinones. The developed UHPLC-UV method revealed high selectivity and a linearity from 1 to 500 µM with correlation coefficients always higher than 0.999. The method has an accuracy that ranged between 89 and 107%, inter-day and intra-day precisions with coefficients of variation below 10%, limits of detection and quantification of 0.31 µM and 0.93 µM for methylone and 0.17 µM and 0.52 µM for pentedrone, respectively. In Caco-2 cells, a differentiated passage of the enantiomers across monolayer was observed for both cathinones. For pentedrone, the difference was observed after the first hour, being R-(-)-pentedrone the most permeable compound. Regarding methylone, the difference was noted after one hour and 30 min, with S-(-)-methylone being the most absorbed enantiomer. In conclusion, a fully validated method was successfully applied for studying the permeability of methylone and pentedrone enantiomers in an in vitro model of human intestine, which allowed to discover, for the first time, the enantioselectivity in drug permeability of this class of drugs.

The potent psychomotor, rewarding and reinforcing properties of 3-fluoromethamphetamine in rodents.

3-fluoromethamphetamine (3-FMA), a derivative of methamphetamine (METH), produces behavioral impairment and deficits in dopaminergic transmission in the striatum of mice. The abuse potential of 3-FMA has not been fully characterized. The aim of this study was to evaluate the effects of 3-FMA on locomotor activity as well as its rewarding and reinforcing properties in the conditioned place preference (CPP) and self-administration procedures. Intravenous (i.v.) administration of 3-FMA (0.5 and 1.0 mg/kg) significantly increased locomotor activity in a dose-dependent manner in rats. In the CPP procedure, intraperitoneal administration of 3-FMA (10 and 30 mg/kg) produced a significant alteration in place preference in mice. In the self-administration paradigms, 3-FMA showed drug-taking behavior at the dose of 0.1 mg/kg/infusion (i.v.) during 2 hr sessions under fixed ratio schedules and high breakpoints at the dose of 0.3 and 1.0 mg/kg/infusion (i.v.) during 6 hr sessions under progressive ratio schedule of reinforcement in rats. A priming injection of 3-FMA (0.4 mg/kg, i.v.), METH (0.2 mg/kg, i.v.), or cocaine (2.0 mg/kg, i.v.) reinstated 3-FMA-seeking behavior after an extinction period in 3-FMA-trained rats during 2 hr session. Taken together, these findings demonstrate robust psychomotor, rewarding and reinforcing properties of 3-FMA, which may underlie its potential for compulsive use in humans.

Determination of the stereoisomeric distribution of R-(-)- and S-(+)-methamphetamine in Thai pills in the legal context of "not inconsiderable quantities".

In Germany, the severity of a narcotic offence is determined based on the classification into different categories of quantity. Recently, an amendment to the Narcotics Law regarding the "not inconsiderable quantities" was introduced. The new limits for methamphetamine are derived from the varying potency of the respective enantiomers. Switzerland, however, does not practice this distinction and there is only one limit quantity, without considering the isomeric structure. To examine whether this single value is still contemporary, 26 Thai pill samples from the years 2000, 2001, 2007, 2009 and 2017 were analyzed by HPLC-MS/MS and GC-MS. Both methods resulted in similar stereoisomeric distributions: the pills mainly consist of the more potent S-(+)-methamphetamine, some even being enantiopure. Others show enantiomeric mixtures of R-(-)-/S-(+)-methamphetamine, but rarely in an equimolar ratio. There even was one sample, where mainly the less potent R-(-)-methamphetamine was detected. In conclusion, the analyses revealed that the single value for a "not inconsiderable quantity" in Switzerland seems outdated. Most of the sized pills showed a much higher concentration of the more potent S-(+)-methamphetamine. The risks related to taking such a pill are much higher and therefore the limit quantity should be adapted to the potency of the respective enantiomers.

In situ electrosynthesis of a copper-based metal-organic framework as nanosorbent for headspace solid-phase microextraction of methamphetamine in urine with GC-FID analysis.

For the first time, a fiber coating based on copper metal-organic framework was fabricated on an anodized stainless steel wire by an in situ electrosynthesis approach. The fiber was used for the preconcentration and determination of methamphetamine by headspace solid-phase microextraction followed by gas chromatography-flame ionization detection. The electrosynthesis of the fiber coating was performed under a constant potential of - 1.7 V by controlling the electrogeneration of OH- in a solution containing sodium nitrate as the probase, 1,2,4,5-benzenetetracarboxylate acid as the ligand and copper nitrate as the cation source. The coating was characterized using field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The effective parameters on the electrosynthesis, extraction, and desorption processes were thoroughly optimized. Under the optimized conditions, metamphetamine (MAP) was quantified over a linear range of 0.90-1000.0 ng mL-1 with R2 > 0.997. A limit of detection of 0.1 ng mL-1 was achieved, and intra- and inter-day relative standard deviations were found within the range 3.0-4.4% and 2.8-3.9%, respectively. Finally, the method was successfully applied to determination of MAP in urine samples with good recoveries in the range 85.0-102.5%. Graphical abstract Schematic representation of the in-situ electrochemical synthesis of a Cu-based metal-organic framework and its application in a headspace SPME procedure for the measuring methamphetamine in urine samples followed by GC-MS analysis.

Enantioseparation and Determination of Mephedrone and Its Metabolites by Capillary Electrophoresis Using Cyclodextrins as Chiral Selectors.

Mephedrone, a psychoactive compound derived from cathinone, is widely used as a designer drug. The determination of mephedrone and its metabolites is important for understanding its possible use in medicine. In this work, a method of capillary electrophoresis for the chiral separation of mephedrone and its metabolites was developed. Carboxymethylated ß-cyclodextrin was selected as the most effective chiral selector from seven tested cyclodextrin derivates. Based on the simplex method, the optimal composition of the background electrolyte was determined: at pH 2.75 and 7.5 mmol·L-1 carboxymethylated ß-cyclodextrin the highest total resolution of a mixture of analytes was achieved. For mephedrone and its metabolites, calibration curves were constructed in a calibration range from 0.2 to 5 mmol·L-1; limits of detection, limits of quantification, precision, and repeatability were calculated, and according to Mandel's fitting test, the linear calibration ranges were determined.

Consequence of Hapten Stereochemistry: An Efficacious Methamphetamine Vaccine.

Recent trends in methamphetamine (METH) misuse and overdose suggest society is inadvertently overlooking a brewing METH crisis. In the past decade, psychostimulant-related lethal overdoses and hospitalizations have skyrocketed 127 and 245%, respectively. Unlike the opioid crisis, no pharmaceutical interventions are available for treating METH use disorder or reversing overdose. Herein, we report the first active vaccine that offers protection from lethal (+)-METH challenge in male Swiss Webster mice. This vaccine formulation of (S)MLMH-TT adjuvanted with CpG ODN 1826 + alum successfully raised anti-METH antibodies in high titers, reduced (+)-METH distribution to the brain, and lowered (+)-METH-associated stereotypies in a hyperlocomotion assay. A comparison of enantiomeric haptens and the racemate elucidated the importance of employing (S)-stereochemistry in METH hapten design for optimal protection.

Trial analysis of drug profiling by liquid chromatography/mass spectrometry and inductively coupled plasma mass spectrometry to establish the origin of ephedrines used as precursors for illicit production of methamphetamine.

RATIONALE: We investigated whether chemical information on the origin of ephedrine and pseudoephedrine (ephedrines) can be acquired by liquid chromatography/mass spectrometry (LC/MS) as a substitute method for stable isotope ratio mass spectrometry (IRMS), which is not routinely available in forensic laboratories. We examined the characteristic inorganic elemental contaminants of ephedrines as a preliminary study. METHODS: The stable isotope ratios measured by IRMS analysis are expressed relative to the stable isotope ratios of conventional standards. Referring to the method using validated standard samples in IRMS, we selected a standard sample for acquiring stable isotopic ratio by LC/MS. The abundance ratio of the [M + 2H]+ ion to the [M + H]+ ion was measured by means of selected ion monitoring. We carried out qualitative analysis of inorganic elements contained in ephedrines produced by different manufacturing methods with ICPMS. RESULTS: We found that the ratio of stable isotope ion to molecular ion (stable isotope ratio) of ephedrines could be measured with LC/MS. The stable isotope ratio of ephedrines determined by LC/MS were confirmed to show relatively good correlations with the carbon and hydrogen stable isotope ratios found by IR-MS. We identified strontium as a characteristic inorganic element contained in ephedrines prepared by the semisynthetic method from molasses, or in the biosynthetic method from ephedra plants. CONCLUSIONS: Our results suggest that useful chemical information can be obtained by LC/MS, which is easy to carry out, and is generally available in forensic laboratories. It would be worthwhile to investigate the usefulness of stable isotope ratio measurements of Sr in the future.

Chromatographic separation of R-(-)/S-(+)-enantiomers of amphetamine and methamphetamine: differentiation between single methamphetamine consumption and co-consumption with amphetamine using enantioselective quantitative LC-MS/MS analysis.

The differentiation between single methamphetamine consumption and co-consumption with amphetamine is difficult, however possible by enantioselective analysis due to different preferred synthesis pathways of both substances. We quantified (R)-(-) and (S)-(+)-enantiomers of methamphetamine and amphetamine by a fast liquid chromatographic tandem-mass spectrometric method using a Lux® 3-µm AMP 150 × 3.0 mm analytical column after simple protein precipitation with methanol. Method validation for quantitative detection showed limits of quantification < 5 ng/mL, linearity in a range between 5 and 300 ng/mL and bias and imprecision data < 15%. Overall, 134 plasma samples of police cases from the German regions of Franconia and Northrhine-Westphalia were analyzed for the enantiomers of methamphetamine and amphetamine. In 28 cases, the intake of racemic illicit amphetamine could be demonstrated; (R)-(-) / (S)-(+)-amphetamine concentration ratios in these cases were between 1.38 and 4.50 with most of the ratios being < 2.0. These ratios were compared to a subgroup of 25 consumers with a co-consumption of (S)-(+)-methamphetamine and racemic amphetamine detected by the qualitative proof of (R)-(-)-amphetamine but also by (R)-(-) / (S)-(+)-amphetamine concentration ratios (< 1 in 11 of 25 cases). Within our collective of 106 plasma samples after methamphetamine use, 25 samples showed co-consumption with amphetamine which shows that co-consumption of both stimulants is not a rare scenario. Furthermore, we could show that if non-stereoselective methods are used and the concentration ratio of total methamphetamine/total amphetamine is determined, a reliable estimation of co-consumption is not possible.

Syndemic and Synergistic Effects of Intimate Partner Violence, Crystal Methamphetamine, and Depression on HIV Sexual Risk Behaviors among Women Who Inject Drugs in Indonesia.

Women who inject drugs are disproportionately affected by co-occurring intimate partner violence (IPV), poor mental health, and substance use. Less is known about the potentially synergistic effects of these factors on women's HIV risk behavior, and no known studies in Asia examine these relationships. This study assessed the additive and interactive effects of exposure to syndemic IPV, depressive symptoms and non-injection crystal methamphetamine (crystal meth) on HIV sexual risk behaviors in the largest cross-sectional sample of women who inject drugs in Indonesia. Seven hundred thirty-one women aged ≥ 18 years, injecting drugs in the preceding 12 months, and residing in Greater Jakarta or Bandung, West Java, were recruited using respondent-driven sampling (RDS). Twenty-six percent of women experienced concurrent IPV, crystal meth use and depressive symptoms. In multivariate logistic regressions controlling for sociodemographic confounders, all three factors were significantly positively associated with sexual risk outcomes. In adjusted marginal effects models, concurrent experience of IPV, crystal meth use and depressive symptoms was associated with increases in the prevalence of HIV risk outcomes: STI symptomatology (from 12% to 60%), inconsistent condom use (from 3% to 22%), and engagement in survival sex work (from 6% to 25%). Statistically significant interaction was detected on both multiplicative and additive scales. Specifically, an interaction was observed on the multiplicative scale between depressive symptoms and crystal meth on STI symptomatology (OR = 2.61; 95% CI = 1.24, 5.48; p = 0.011). There was also evidence of additive interaction, with most observed joint effects being greater than additive. Specifically, significant positive interaction was observed between IPV and crystal meth on inconsistent condom use (AP = 0.38, p < 0.05); depressive symptoms and crystal meth on STI symptomatology (RERI = 2.04, p < 0.001; AP = 0.61, p < 0.001) and survival sex (RERI = 1.20, p < 0.01; AP = 0.53, p < 0.01); and IPV and depressive symptoms on STI symptomatology (RERI = 3.01, p < 0.01; AP = 0.52, p < 0.001; S = 2.70, p < 0.01) and survival sex (RERI = 1.21, p < 0.05; AP = 0.40, p < 0.05). This study provides new empirical evidence showing that the syndemic conditions of IPV, depressive symptoms and crystal meth consumption interact synergistically to increase women's HIV risk. Interventions that consider the full scope of syndemic vulnerabilities, rather than addressing individual conditions separately, may be essential.

Epoxide-derived mixed-mode chromatographic stationary phases for separation of active substances in fixed-dose combination drugs.

A method for the preparation of novel mixed-mode reversed-phase/strong cation exchange stationary phase for the separation of fixed-dose combination drugs has been developed. An epoxysilane bonded silica prepared by vapor phase deposition was used as a starting material to produce diol, octadecyl, sulfonate, and mixed octadecyl/sulfonate groups bonded silica phases. The chemical structure and surface coverage of the functional groups on these synthesized phases were confirmed by fourier-transform infrared and solid-state 13 C NMR spectroscopy and elemental analysis. Alkylbenzene homologs, basic drugs, nucleobases and alkylaniline homologs were used as probes to demonstrate the reversed-phase, ion exchange, hydrophilic interaction and mixed-mode retention behaviors of these stationary phases. The octadecyl/sulfonate bonded silica exhibits pronounced mixed-mode retention behavior and superior retentivity and selectivity for alkylaniline homologs. The mixed-mode retention is affected by either ionic or solvent strength in the mobile phase, permiting optimization of a separation by fine tuning these parameters. The mixed-mode stationary phase was applied to separate two fixed-dose combination drugs: compound reserpine tablets and compound methoxyphenamine capsules. The results show that simultaneous separation of multiple substances in the compound dosage can be achieved on the mixed-mode phase, which makes multi-cycles of analysis for multiple components obsolete.