Heptafluorobutyric Anhydride Research Articles

GC-MS analysis of eight aminoindanes using three derivatization reagents.

Aminoindanes are a class of novel psychoactive substances (NPSs) that have become more prevalent over the past decade. GC-MS is often utilized for identifying seized drugs and is well regarded for its ability to separate mixtures. However, certain aminoindanes have similar mass spectral data and require specific gas chromatographic stationary phases for separation. Derivatization is an alternative method that can be applied to GC-MS to enhance chromatographic results, providing more selective analysis in seized-drug identification. This study investigates derivatization techniques to provide options for forensic science laboratories in accurately identifying aminoindanes. Three derivatization reagents, N-methyl-bis(trifluoroacetamide) (MBTFA), heptafluorobutyric anhydride (HFBA), and ethyl chloroformate (ECF) were evaluated for the analysis of eight aminoindanes by GC-MS using two common gas chromatographic stationary phases, Rxi®-5Sil MS and Rxi®-1Sil MS. All three derivatization methods successfully isolated eight aminoindanes, including the isomers 4,5-methylenedioxy-2-aminoindane (4,5-MDAI), and 5,6-methylenedioxy-2-aminoindane (5,6-MDAI) that could not be differentiated prior to derivatization. Reduced peak tailing and increased abundance were observed after derivatization for all the compounds, and mass spectra of the derivatives contained individualizing fragment ions that allowed for further characterization of the aminoindanes. This excluded 4,5-MDAI and 5,6-MDAI as they shared the same characteristic ions and were only distinguishable by their retention times. All three derivatization techniques used in this study allow for successful characterization of the aminoindanes and give forensic science laboratories flexibility in their analysis approach when they encounter these compounds.

Molecularly imprinted conjugated microporous polymer composite as solid phase extraction adsorbent for the extraction of phenolic endocrine disrupting chemicals in beverages

A molecularly imprinted triazine-based conjugated microporous polymer composite with rich porosity and good selectivity was prepared and used as the adsorbent of solid-phase extraction (SPE). The composite-based SPE for the three phenolic endocrine disrupting chemicals (nonylphenol, octylphenol and bisphenol A) in different beverages followed by derivatization with heptafluorobutyric anhydride and then detection by gas chromatography-electron capture detector was developed. The variables mainly affecting the extraction and derivatization were evaluated. Under the optimal conditions, the limits of detection (S/N = 3) of the established method for the analytes ranged from 0.12 to 1.20 µg L−1. The linear response range of the method was 0.40–50.0 µg L−1, with the coefficients of determination falling in the range of 0.9906–0.9994. The relative recoveries of the phenolic endocrine disrupting chemicals in spiked beverage samples at three concentration levels (high, middle, and low) were in the range of 80.6% −117% with the relative standard deviations of 3.5%-11%. The established method exhibits a potential in the monitoring of trace phenolic endocrine disrupting chemicals in real beverage samples.

Determination of 3-chloro-1,2-propanediol in biological samples by quick-easy-cheap-effective-rugged-and-safe extraction coupled with gas chromatography-mass spectrometry and its biodistribution in rats.

3-Chloro-1,2-propanediol is a common food contaminant, but reports on its determination in biological tissues are lacking. In the present study, a method was developed to detect 3-chloro-1,2-propanediol contents in rat tissues by quick-easy-cheap-effective-rugged-and-safe extraction and gas chromatography-mass spectrometry analysis. Biological samples were extracted with ethyl acetate and purified with adsorbents. The optimized adsorbent for each sample was selected from 4-5 combinations of N-propylethylenediamine, octadecylsilane, graphitized carbon black, strong anion exchange, and florisil. Extracted 3-chloro-1,2-propanediol was derivatized with heptafluorobutyric anhydride and subjected to gas chromatography-mass spectrometry. This method had good linearity (correlation coefficients>0.99) in the range of 2-2000ng/g for blood, kidney, liver, testis, and brain samples. The limits of detection were under 0.8ng/g; the limits of quantification were 2ng/g; the recovery rates were 85%-102%; and the matrix effects were 1.98%-7.67%. This method also had good precision. The dynamic changes in 3-chloro-1,2-propanediol in rats gavaged with 20mg/kg b.w. for 24h were detected using this method. The 3-chloro-1,2-propanediol content in each tissue sharply increased to a peak, rapidly decreased within 2h, and stabilized at 12h. 3-Chloro-1,2-propanediol persisted in the kidney, testis, and liver 24h after gavage.

Probing the binding interactions between perfluoroalkyl carboxylic acids and adenosine A2A receptors by spectroscopic techniques, molecular simulations and quantum chemistry

The binding interactions of perfluorobutyric acid (PFBA), heptafluorobutyric anhydride (HFBA), and ethyl heptafluorobutyrate (NSC3936) with the adenosine A2A receptor (A2AR) were investigated using multiple-spectral (fluorescence, ultraviolet–visible (UV–Vis) absorption, three-dimensional (3D) fluorescence, and Fourier Transform infrared (FT-IR) spectroscopy) and computational simulation methods. Steady-state fluorescence and UV–visible spectroscopy indicated that PFBA, HFBA, and NSC3936 caused an intrinsic fluorescence quenching of A2AR by static quenching and non-radiative energy transfer. The results of 3D fluorescence and FT-IR spectroscopy showed that the presence of PFBA, HFBA, and NSC3936 induced changes in the secondary structure of A2AR. Combined with thermodynamic analysis, molecular docking and quantum chemistry investigations, our results suggest that the association of PFBA, HFBA, and NSC3936 with A2AR was driven by hydrophobic forces and the formation of hydrogen bonds (H-bonds). The binding constants for the three PFCAs studied range from 8.27 × 106 L·mol−1 to 1.80 × 107 L·mol−1 at 298 K. Molecular dynamics (MD) simulations indicated that A2AR formed stable complexes with PFBA, HFBA, and NSC3936, and validated the existence of electrostatic interactions in the HFBA-A2AR complex. Furthermore, the results from the MD simulations were consistent with the thermodynamic analysis results.

Fluorinated carboxymethyl chitosan-based nano-prodrugs for precisely synergistic chemotherapy

The clinical transformation of polysaccharide-based nano-prodrugs remains a long way off, due to the shackles on easy metabolic clearance, dilemma of dose-dependent toxicity and immunogenicity, and poor tumor selectivity. To address these challenges, the fluorinated dual-crosslinked carboxymethyl chitosan (CMCS)-based nano-prodrugs with precise structure were facilely developed through the reaction of CMCS with water-soluble stimuli-responsive synergistic small molecule prodrug (Pt(IV)-1), glutaraldehyde and heptafluorobutyric anhydride successively. The fluorination enabled the nano-prodrugs to display metabolic stability and improve tumoral cellular uptake. The pH/glutathione (GSH)-sensitive dual-crosslinked structure enabled the nano-prodrugs to show physicochemical stability at physiological pH, selective drug release and synergistic cytotoxicity at tumoral intracellular pH/GSH, and circumventing the dilemma of dose-dependent toxicity and immunogenicity induced by that crosslinked or grafted via a single drug. These superior performances promoted stability in long-term storage and circulation, normal blood routine and aminotransferase, fantastic hemocompatibility, selective tumor accumulation and precisely synergistic chemotherapy, therefore achieving significant tumor growth inhibition while minimizing side effects. Thus, the precise fluorinated dual-crosslinked CMCS-based nano-prodrugs have great potential for selective clinical cancer treatment.

ROS responsive polyethylenimine-based fluorinated polymers for enhanced transfection efficiency and lower cytotoxicity.

Cationic polymer polyethylenimine (PEI) plays a crucial role in gene delivery. However, high molecular weight PEI leads to higher efficient transfection efficacy and higher cytotoxicity, while low molecular weight PEI exhibits lower transfection performance with lower toxicity. Therefore, effective chemical modification of PEI is required to enhance transfection activity and improve biocompatibility. Here, reactive oxygen species (ROS) responsive PEI-based fluorinated polymers (TKPF) with three degrees of fluorination (TKPF 12.5%, TKPF 25%, and TKPF 50%) were designed and synthesized by crosslinking low molecular weight PEI (PEI 1.8K) with a thioketal (TK) linker and then modifying heptafluorobutyric anhydride onto their surface. Fluorination reduced the positive charge density and endowed hydrophobic and lipophobic characteristics to resist serum interactions. The fluorophilic effect mediated efficient cellular uptake and endosomal escape while ROS-responsive TK linker allowed the polyplex disassembly to decrease the cytotoxicity of the polycations and improve the release of payloads at specific sites. TKPFs attained superior transfection efficiency in multiple cell lines (293TN cells and B16F10 cells) in vitro and showed excellent biocompatibility. TKPFs also exhibited great serum resistance in gene delivery and TKPF 50% transfected nearly 80% cells in the presence of 70% FBS. These results demonstrate that the fluorination and ROS responsiveness combined polycations are excellent gene-delivery vectors with serum-resistant capacity for further application.

Powerful qua-functional electrolyte additive for lithium metal batteries

Lithium metal batteries (LMBs) have attracted tremendous research attention because of the high theoretical capacity (3860 mAh g−1) and the lowest electrochemical potential (−3.04 V vs. standard hydrogen electrode). However, the Lithium dendrites, forming from plating/stripping processes, cause the excessive consumption of electrolyte and active Li and the puncture on the separator. This limits the commercialization of LMBs. Recently, Ma's group proposed heptafluorobutyric anhydride (HFA) as qua-functional electrolyte additive and verified the protection mechanism from the structure and electrochemical properties. Such results creatively put forward qua-functional electrolyte additive for the improvement of LMBs and provides good experience for the exploration of multi-functional additive, inspiring researchers to explore new multi-functional electrolyte additives in future.

Optimizing Electrode/Electrolyte Interphases and Li‐Ion Flux/Solvation for Lithium‐Metal Batteries with Qua‐Functional Heptafluorobutyric Anhydride

AbstractThe safety and electrochemical performance of rechargeable lithium‐metal batteries (LMBs) are primarily influenced by the additives in the organic liquid electrolytes. However, multi‐functional additives are still rarely reported. Herein, we proposed heptafluorobutyric anhydride (HFA) as a qua‐functional additive to optimize the composition and structure of the solid electrolyte interphase (SEI) at the electrode/electrolyte interface. The reduction/oxidation decomposition of the fluorine‐rich HFA facilitate uniform inorganic‐rich SEI and compact cathode electrolyte interphase (CEI) formation, which enables stable lithium plating during charge and suppresses the dissolution of transition‐metal ions. Moreover, HFA optimizes the Li‐ion solvation for stable Li plating/stripping and serves as the surfactant to enhance the wettability of the separator by the electrolyte to increase Li‐ion flux. The symmetric Li∥Li cell with 1.0 wt % HFA electrolyte had an excellent cycling performance over 340 h at 1.0 mA cm−2 with a capacity of 0.5 mAh cm−2 while the Li∥NCM622 cell maintained high capacity retention after 250 cycles and outstanding rate performance even at 15 C.

Optimizing Electrode/Electrolyte Interphases and Li-Ion Flux/Solvation for Lithium-Metal Batteries with Qua-Functional Heptafluorobutyric Anhydride.

The safety and electrochemical performance of rechargeable lithium-metal batteries (LMBs) are primarily influenced by the additives in the organic liquid electrolytes. However, multi-functional additives are still rarely reported. Herein, we proposed heptafluorobutyric anhydride (HFA) as a qua-functional additive to optimize the composition and structure of the solid electrolyte interphase (SEI) at the electrode/electrolyte interface. The reduction/oxidation decomposition of the fluorine-rich HFA facilitate uniform inorganic-rich SEI and compact cathode electrolyte interphase (CEI) formation, which enables stable lithium plating during charge and suppresses the dissolution of transition-metal ions. Moreover, HFA optimizes the Li-ion solvation for stable Li plating/stripping and serves as the surfactant to enhance the wettability of the separator by the electrolyte to increase Li-ion flux. The symmetric Li∥Li cell with 1.0 wt % HFA electrolyte had an excellent cycling performance over 340 h at 1.0 mA cm-2 with a capacity of 0.5 mAh cm-2 while the Li∥NCM622 cell maintained high capacity retention after 250 cycles and outstanding rate performance even at 15 C.

Investigation on amitraz, coumaphos and thymol concentrations in honey produced by Slovenian beekeepers in 2020

A survey on concentrations of veterinary drug residues amitraz, coumaphos and thymol in honey, produced in year 2020 by Slovenian beekeepers, was conducted. 100 samples were analysed: 22 from organic and 78 from conventional production, with two analytical methods. In method for determination of coumaphos and thymol samples were extracted with acetone, petroleumether and dichlorometane. In method for determination of amitraz and its degradation products, samples were hydrolisated with HCl and NaOH, extractied with n-hexane and derivatisated with heptafluorobutyric anhydride. Determination in both methods was performed with gas chromatograph coupled with mass spectrometer. Measured concentrations of amitraz, coumaphos and thymol were in the range of 0.01-0.12 mg kg-1, 0.02-0.06 mg kg-1 and 0.08-0.17 mg kg-1, respectively. In 61 % of samples analysed no residues of amitraz, thymol and coumaphos were found. Data obtained were compared with the data from literature. Chronic and acute exposure were calculated for consumers. Maximum chronic exposure for amitraz and thymol was 0.1 % and 0.05 % of acceptable daily intake, respectively. Maximum acute exposure for amitraz and thymol was 4 % and 0.8 % of acute reference dose, respectively

Fluoropolymer‐Mediated Intracellular Delivery of miR‐23b for the Osteocyte Differentiation in Osteoblasts

Emerging evidence suggests that microRNAs (miRNAs) play key roles in the regulation of multiple biological processes, including the differentiation of osteoblasts. Although miRNA-based gene therapy holds immense potential in the treatment of a variety of diseases, the intracellular delivery of miRNA remains challenging owing to the lack of efficient and safe gene carriers. In this study, a fluoropolymer (FP) is constructed through the modification of polyamidoamine (PAMAM) using heptafluorobutyric anhydride and then is used as a carrier for miR-23b transfection to induce osteocyte differentiation of osteoblasts. The derivative FP is found to facilitate miR-23b transfection due to its favorable endosomal escape from the "proton sponge" effect. Compared to PAMAM/miR-23b, the FP/miR-23b nanocomplex efficiently promotes the differentiation of osteoblasts and formation of calcified nodules, attributable to enhanced expression of various osteogenesis genes (runt-related transfection factor 2 [RUNX2], alkaline phosphatase [ALP], osteopontin [OPN], and osteocalcin [OCN]). Thus, FP-mediated miR-23b transfection may be used as an effective strategy to facilitate osteogenic differentiation.

Determination of zolpidem phenyl-4-carboxylic acid and zolpidem 6-carboxylic acid in hair using gas chromatography-electron ionization-tandem mass spectrometry.

A gas chromatography-electron ionization-tandem mass spectrometric (GC-EI-MS/MS) method was developed and validated for determination of the major metabolites of zolpidem, zolpidem phenyl-4-carboxylic acid (ZPCA) and zolpidem 6-carboxylic acid (ZCA) in human hair. The sample preparation procedure involves decontamination, mechanical pulverization, incubation, extraction and purification prior to instrumental analysis. The extracts were derivatized using hexafluoroisopropanol and heptafluorobutyric anhydride and analyzed by GC-EI-MS/MS. The linear ranges were 8-100 pg/mg for ZPCA and 16-200 pg/mg for ZCA, with the correlation coefficients >0.997. The limits of detection were 1.8 pg/mg for ZPCA and 1.7 pg/mg for ZCA. The recoveries ranged from 77.6 to 111.7%. The intra- and inter-day precisions were within 16.9 and 11.7%, while intra- and inter-day accuracies were -7.0-8.7 and -2.8-7.8%, respectively. The developed method was applied for the analysis of forensic hair samples obtained from suspected zolpidem abusers and the following concentration ranges were monitored: ZPCA 11.9-35.9 pg/mg and ZCA 16.6-21.8 pg/mg. The method proved to be suitable for picogram-level determination of ZPCA and ZCA in human hair.

Study of the distribution of antidepressant drugs in vitreous humor using a validated GC/MS method

Vitreous humor has become in recent years an important alternative biological fluid in forensic toxicological analysis especially for the investigation of cases where alcohol and drugs of abuse are involved but there is limited scientific information regarding the distribution of antidepressant drugs in this material. This work aimed to study the distribution of antidepressant drugs in vitreous humor and to estimate the blood/vitreous humor concentration ratios of these drugs. For this purpose, a GC/MS method for the simultaneous determination of 9 antidepressant drugs, namely amitriptyline, nortriptyline, citalopram, clomipramine, fluoxetine, maprotiline, mirtazapine, sertraline and venlafaxine, and 4 of their metabolites, namely desmethylmaprotiline, desmethylmirtazapine, desmethylsertraline, O-desmethylvenlafaxine, was developed and validated. The developed method includes solid-phase extraction followed by derivatization with Heptafluorobutyric Anhydride. For all analytes, LOD and LOQ were 1.50 and 5.00ng/mL, respectively, and the calibration curves were linear within the dynamic range of 5.00–500.0ng/mL (R2≥0.990). The absolute recovery was found to be ≥86.3 % for all analytes. The accuracy (%Er) was found to range between -6.58 and 6.18 %, whereas the precision (%RSD) was less than 10.9 % for all analytes. The developed method was successfully applied to vitreous humor samples from 43 blood positive cases for antidepressant drugs. Whenever antidepressant drugs were detected in blood, they were also detected in the respective vitreous humor samples. The vitreous humor/blood concentration ratios were also calculated and were found to range from 0.04–7.07. Citalopram, mirtazapine, and its metabolite desmethylmirtazapine as well as venlafaxine and its metabolite O-desmethylvenlafaxine were the most identified substances in these samples (n≥4) and their results were better statistically evaluated. Our results suggest that vitreous humor could be an appropriate matrix for the determination of antidepressants in postmortem toxicology.

Determination of Amphetamine and Methamphetamine in Human Hair by Gas Chromatography Mass Spectrometry

This article develops a combined solid phase extraction (SPE) and gas chromatography – mass spectrometry (GC-MS) procedure for determining amphetamine-type stimulants Amphetamine (AM) and Methamphetamine (MA) in human hair. Hair samples were incubated in methanol containing 1% hydrochloric acid in 18 hours and then subjected to SPE. The obtained extracts were evaporated to dryness, derivatized with heptafluorobutyric anhydride (HFBA) at 70 °C for 30 minutes prior to GC–MS analysis. Gas chromatography mass spectrometry was run on HP5-MS column (30 m × 0.25 mm × 0.25 µm) with detector MS 5975C. Experimentally, the proposed method proved sensitive, simple and time-saving, but quite accurate with a low limit of detection (LOD = 0.05ng/mg) and quantitation (LOQ = 0.15ng/mg).
 Keywords:
 SPE, GC – MS, hair samples, amphetamine, methamphetamine.
 References
 [1] Ming-Ren Fuh, Ti-Yu Wu and Tzuen-Yeuan Lin, Determination of amphetamine and methamphetamine in urine by solid phase extraction and ion-pair liquid chromatography–electrospray–tandem mass spectrometry Talanta, 68 (3) (2006), 987-991. https://doi.org/10.1016/j.talanta.2005.06.057[2] Naresh C. Jain, Thomas C. Sneath, and Robert D. Budd, Rapid Gas-Chomatographic Determination of Amphetamine and Methamphetamine in urine, Clinical Chemistry, 20 (11) (1974) 1460-1462. https://doi.org/10.1093/clinchem/20.11.1460.[3] Dong-liang Lin, Rea-Ming Yin, Ray H. Liu, Gas Chromatography-Mass Spectrometry (GC-MS) Analysis of Amphetamine, Methamphetamine, 3,4-Methylenedioxy- amphetamine and 3,4-Methylenedioxymethamphetamine in Human Hair and Hair Sections, Journal of Food and Drug Analysis, 13(2) (2005) 193-200. https://doi.org/10.38212/2224-6614.2526[4] María Jesús Tabernero, Maria Linda Felli, Ana María Bermejo, Marcello Chiarotti, Determination of ketamine and amphetamines in hair by LC/MS/MS, Anal Bioanal Chem, 395(2009), 2547–2557. https://doi.org/10.1007/s00216-009-3163-4.[5] D.V. Doan, D.Q. Huy, N.D. Hue, T.M. Tri, Determination of methamphetamine in urine samples by gas chromatography mass spectrometry combined with solid phase extraction technique, Journal of Science and Technology 47 (6) (2009) 53-58 (in Vietnamese).[6] Rodger L. Foltz, Allison F. Fentiman, Ruth B. Foltz, GC/MS Assays for Abused Drugs in Body Fluids, National Institute on Drug Abuse, Maryland, 1980.[7] AOAC, Appendix F: Guidelines for Standard Method Performance Requirements, AOAC official methods of analysis, Maryland, 2016.[8] Eunyoung Han, Martin P. Paulus, Marc Wittmann, Heesun Chung, Joon myong Song, Hair analysis and self-report of methamphetamine use by methamphetamine dependent individuals, Journal of Chromatography B, 879 (2011) 541–547. https://doi.org/10.1016/j.jchromb.2011.01.002.
 
 

“Building-block crosslinking” micelles for enhancing cellular transfection of biocompatible polycations

Incorporating functional ligands and biodegradable bonds into biocompatible low-molecular-weight (LMW) polymers, such as 1.8 kDa poly(ethylenimine) (PEI 1.8k), is a common strategy to improve the properties of LMW polymers including biosafety and delivery efficacy. This study demonstrates the hypothesis that introducing different functional ligands and linked reductive disulfides in PEI 1.8k will achieve superior siRNA transfection efficiency. By incorporating PEI-X (X represents cholesterol (Ch), heptafluorobutyric anhydride (HFBA, F) and 4-carboxyphenyl-boronic acid (PBA)) functional ligands into PEI 1.8k and subsequently crosslinking with each other via disulfide bond links, reductive-responsive PEI-X-SS-X-PEI copolymers were constructed to enhance the cellular transfection via the synergistic effect of the high affinity of Ch, F and PBA to cell membranes and the disulfide reduction triggered intracellular disassembly of micelles and subsequent siRNA release. Extraordinarily, ternary Ch-SS-F-SS-PBA micelles exhibited the strongest siRNA transfection efficiencies in in vitro cell experiments and in vivo animal experiments due to the coordination of enhanced serum stability, promoted cell uptake and endosomal escape, and cell targeting ability. This strategy of constructed multifunctional polymer here we called “building-block crosslinking” showed a simple and smart way to synthesize new materials. Also this strategy of constructing ligands-directed reduction-sensitive micelles improves the transfection efficiency of LMW PEI and provides a valuable insight to develop novel gene delivery systems.

Identification of a new class of thermolabile psychoactive compounds, 4-substituted 2-(4-X-2, 5-dimethoxyphenyl)-N-[(2-hydroxyphenyl)methyl]ethanamine (25X-NBOH, X = Cl, Br, or I) by gas chromatography-mass spectrometry using chemical derivatization by heptafluorobutyric anhydride (HFBA)

4-Substituted 2-(4-X-2,5-dimethoxyphenyl)-N-[(2-hydroxyphenyl)methyl] ethanamine (25X-NBOH, X = Cl, Br, or I) are new psychoactive substances (NPS). Identification of these NBOH analogues by gas chromatography-mass spectrometry is difficult because they are found in very low concentrations in the blotting paper in which they are sold, and because of the thermolabile nature of NBOH. In the ion source of a mass spectrometer they break down to the known NPS 2,5-dimethoxy-4-Xphenethylamine (2C-X) thereby giving no indication of the initial compound present. We identify 25XNBOH by heptafluorobutyric anhydride (HFBA) derivatization and subsequent mass spectrometric analysis. The major peak is the bis-derivative where both the amine and phenol are derivatized, with a minor peak of the mono-derivative in which only the amine is derivatized. There is a small amount of degradation of 25X-NBOH to the 2C-X amine which is then derivatized to the amide in-situ. Reaction with HFBA is an efficient and simple derivatization that works well with NBOH and NBOMe analogs and is recommended for routine forensic analysis.

Gas chromatography-mass spectrometry (GC-MS) analysis of amphetamine, methamphetamine, 3,4-methylenedioxy-amphetamine and 3,4-methylenedioxymethamphetamine in human hair and hair sections

In this paper, the authors describe a sensitive method for simultaneous quantitation of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) in human hair by gas chromatography-mass spectrometry (GC-MS). Hair samples are initially cut into 0.5-cm sections, washed with methanol, and digested for 1 hr at 80°C in 2 N NaOH and deuterated internal standards. The resulting solutions are processed with a liquid-liquid extraction procedure and further derivatized with heptafluorobutyric anhydride (HFBA) before undergoing GC/MS analysis. The overall protocol achieves the following results when applied to the analysis of 50 mg drug-free hair specimens fortified with 2-40 ng/mg amphetamines: recovery: 77.45-86.86%; inter-day and intra-day precision ranges: 0.55-7.73% and 0.76-4.79%, respectively; linearity: r2 > 0.997; detection limits: 0.05 ng/mg for AM, MA, and MDMA and 0.1 ng/mg for MDA; and quantitation limits: 0.1 ng/mg for AM, MA, and MDMA and 0.2 ng/mg for MDA. Data derived from our analysis of hair samples collected from 30 self-reported methamphetamine abusers range from 1.39 to 15.41 (mean ± S.D., 5.21 ± 3.25) ng/mg for amphetamine and 12.58 to 173.28 (mean ± S.D., 56.10 ± 36.85) ng/mg for methamphetamine. This method has also been utilized successfully to evaluate the deposition pattern of drugs in head hairs collected from six female methamphetamine abusers staying at a rehabilitation facility. We conclude that this relatively simple protocol can be used for routine and reliable identification and quantitation of AM, MA, MDA, and MDMA in hair.

NeuroDefend, a novel Chinese medicine, attenuates amyloid-β and tau pathology in experimental Alzheimer's disease models

Higenamine (HG), a cardioactive component of some foods and medicines, has been listed in the doping category by the International Olympic Committee, which may lead to misuse by athletes. We report the development of a gas chromatography-mass spectrometry (GC–MS) method for determination of HG in various matrix samples (biological samples, different forms of Chinese patent medicine, Chinese herbal medicine) based on acylation derivatization of HG by heptafluorobutyric anhydride. Under optimal conditions, the linearity of HG in the range of 5–200 ng mL−1 was acceptable (R2 > 0.999), and the limit of detection (LOD) and limit of quantitation (LOQ) for HG was 1.52 ng mL−1 and 5 ng mL−1, respectively. Low, medium, and high concentrations (25, 100 and 160 ng mL−1) of HG were added to plasma, urine, oral liquid, capsule, watered bolus, honeyed bolus and Chinese herbal medicine samples, with recovery ranging from 82.70 to 109.80%, intra-day and inter-day precisions were both less than 3.39%. The results indicated that the method had sufficient sensitivity for analysis of biological samples, and Chinese patent and herbal medicine. © 2019

The effects of fluoroalkyl chain length and density on siRNA delivery of bioreducible poly(amido amine)s

Fluorination is an attractive strategy for the improvement of transfection efficiency of nucleic acid delivery vectors. Bioreducible poly(amido amine)s (bPAAs) are an important class of biomaterials exhibited to effectively deliver multiple nucleic acids. However, still, the effects of fluoroalkyl chain length and density of bPAA on siRNA delivery are unveiled. Here, we synthesized bPAAs and grafted with different chain lengths and densities of fluorocarbon compounds. Furthermore, we prepared a library of complexes of fluorinated bPAA and siRNA, and investigated the effects of fluorination on the siRNA delivery in vitro and in vivo. We found that all the synthesized bPAAs readily formed complexes with siRNA and the fluorinated complexes considerably achieved improved gene silencing efficacies both in vitro and in vivo. Dramatically, the gene silencing efficacy was increased with increasing fluorine contents. Heptafluorobutyric anhydride (HF) modified bPAAs achieved better gene silencing efficacy when compared with bPAAs fluorinated by trifluoroacetic anhydride (TF) and pentafluoropropionic anhydride (PF) providing the evidence for choosing of best one among fluorocarbon compounds. In addition, a combination of fluorination with bioreducibility enables efficient and safe siRNA delivery.

Syntheses and analytical characterizations of novel (2-aminopropyl)benzo[b]thiophene (APBT) based stimulants.

Two groups of amphetamine-like drugs with psychostimulant properties that were first developed during the course of scientific studies and later emerged as new psychoactive substances (NPS) are based on the (2-aminopropyl)indole (API) and (2-aminopropyl)benzofuran (APB) structural scaffolds. However, sulfur-based analogs with a benzo[b]thiophene structure (resulting in (2-aminopropyl)benzo[b]thiophene (APBT) derivatives) have received little attention. In the present investigation, all six racemic APBT positional isomers were synthesized in an effort to understand their structure-activity relationships relative to API- and APB-based drugs. One lesson learned from the NPS phenomenon is that one cannot exclude the appearance of such substances on the market. Therefore, an in-depth analytical characterization was performed, including various single- and tandem mass spectrometry (MS) and ionization platforms coupled to gas chromatography (GC) and liquid chromatography (LC), nuclear magnetic resonance spectroscopy (NMR), and solid phase and GC condensed phase infrared spectroscopy (GC-sIR). Various derivatizations have also been explored; it was found that all six APBT isomers could be differentiated during GC analysis after derivatization with heptafluorobutyric anhydride and ethyl chloroformate (or heptafluorobutyric anhydride and acetic anhydride) under non-routine conditions. Discriminating analytical features can also be derived from NMR, GC-EI/CI- single- and tandem mass spectrometry, LC (pentafluorophenyl stationary phase), and various infrared spectroscopy approaches (including GC-sIR). Availability of detailed analytical data obtained from these novel APBT-type stimulants may be useful to researchers and scientists in cases where forensic and clinical investigations are warranted.