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Background: Naphthylamine (NA), i.e., 1-naphthylamine (1-NA) and 2-naphthylamine (2-NA) and its salts (2-naphthylamine hydrochloride and 2-naphthylamine acetate) are colorless crystalline solids. They have been used, among others, in the production of paints and dyes. In the European Union, 1-NA is classified as a toxic substance, and 2-NA and its salts as carcinogenic category 1A. The aim of this study was to develop a new method for the determination of NA, which will enable the determination of 1-NA and 2-NA and its salts in the working environment, in the concentration range of 0.3-6 μg/m 3 ., Material and Methods: The method consists in passing the test air containing the substances to be determined through a glass fiber filter impregnated with sulphuric acid(VI). After recovery with water and sodium hydroxide solution followed by extraction into a solid on Oasis HLB columns, the solutions in methanol are analyzed using a high-performance liquid chromatograph with a fluorescence detector and Ultra C18 column., Results: The method developed allows determining 1-NA and 2-NA and its salts in the concentration range of 0.3-6 μg/m 3 . The limit of detection for 1-NA is 81 pg/ml and for 2-NA - 80.6 pg/ml., Conclusions: The method is characterized by good precision and accuracy; it meets the requirements of European Standard PN-EN 482 and can be used by occupational hygiene laboratories to measure the level of 1-NA and 2-NA and its salts in workplace air to assess workers' exposure to these substances. Med Pr. 2021;72(2):145-54., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Fluorescent sensors are a vital research tool, enabling the study of intricate cellular processes in a sensitive manner. The design and synthesis of responsive and targeted probes is necessary to allow such processes to be interrogated in the cellular environment. This remains a challenge, and requires methods for functionalisation of fluorophores with multiple appendages for sensing and targeting groups. Methods to synthesise more structurally complex derivatives of fluorophores will expand their potential scope. Most known 4-amino-1,8-naphthalimides are only functionalised at imide and 4-positions, and structural modifications at additional positions will increase the breadth of their utility as responsive sensors. In this work, methods for the incorporation of a hypoxia sensing group to 4-amino-1,8-naphthalimide were evaluated. An intermediate was developed that allowed us to incorporate a sensing group, targeting group, and ICT donor to the naphthalimide core in a modular fashion. Synthetic strategies for attaching the hypoxia sensing group and how they affected the fluorescence of the naphthalimide were evaluated by photophysical characterisation and time-dependent density functional theory. An extracellular hypoxia probe was then rationally designed that could selectively image the hypoxic and necrotic region of tumour spheroids. Our results demonstrate the versatility of the naphthalimide scaffold and expand its utility. This approach to probe design will enable the flexible, efficient generation of selective, targeted fluorescent sensors for various biological purposes., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Naphthoquine (NQ) is one of important partner drugs of artemisinin-based combination therapy (ACT), which is recommended for the treatment of uncomplicated Plasmodium falciparum. NQ shows a high cure rate after a single oral administration. It is absorbed quickly (time to peak concentration 2-4 h) and has a long elimination half-life (255 h). However, the metabolism of NQ has not been clarified. In this work, the metabolite profiling of NQ was studied in six liver microsomal incubates (human, cynomolgus monkey, beagle dog, mini pig, rat and CD1 mouse), seven recombinant CYP enzymes (1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4) and rat (plasma, urine, bile and feces) using liquid chromatography tandem high-resolution LTQ-Orbitrap mass spectrometry (HRMS n ) in conjunction with online hydrogen/deuterium exchange. The biological samples were pretreated by protein precipitation and solid-phase extraction. For data processing, multiple data-mining tools were applied in tandem, i.e. background subtraction and followed by mass defect filter. NQ metabolites were characterized by accurate MS/MS fragmentation characteristics, the hydrogen/deuterium exchange data and cLogP simulation. As a result, five phase I metabolites (M1-M5) of NQ were characterized for the first time. Two metabolic pathways were involved: hydroxylation and N-oxidation. This study demonstrates that LC-HRMS n in combination with multiple data-mining tools in tandem can be a valuable analytical strategy for rapid metabolite profiling of drugs., (Copyright © 2018 John Wiley & Sons, Ltd.)

Objectives: 1,5-Naphthalene diisocyanate (NDI) is used in the plastic industry as a curing agent. 1,5-Naphthalene diisocyanate is classified as a sensitizing agent. The objective of this study has been to develop biomonitoring methods for the evaluation of exposure to NDI., Material and Methods: We obtained blood and urine samples from a group of 20 male workers exposed to NDI. The workers answered a questionnaire about their exposure history, job description, the number of years with the company and the time spent working with NDI over the 10 days of the study. Total plasma, albumin, and urine were analyzed for the presence of 1,5-naphthalenediamine (NDA) after acid hydrolysis using gas chromatography-mass spectrometry (GC-MS)., Results: 1,5-Naphthalenediamine was found in about 60% of the samples obtained from the workers. 1,5-Naphthalenediamine was obtained after acid hydrolysis of plasma, albumin, and urine at levels up to 1.5 pmol NDA/mg of plasma proteins, 1.15 pmol NDA/mg of albumin, and 55.3 pmol NDA/ml of urine, respectively., Conclusions: 1,5-Naphthalenediamine found in urine correlates best with the plasma levels (r = 0.91, p < 0.01). The albumin-adduct levels did not correlate with the NDI-specific immunoglobulin E (IgE) or total IgE present in the workers. The adduct and metabolite levels correlate with the air levels of NDI. Int J Occup Med Environ Health 2017;30(4):579-591., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

A fully automated, rapid, and reliable method for simultaneous determination of six carcinogenic primary aromatic amines (AAs), including o-toluidine (o-TOL), 2, 6-dimethylaniline (2, 6-DMA), o-anisidine (o-ASD), 1-naphthylamine (1-ANP), 2-naphthylamine (2-ANP), and 4-aminobiphenyl (4-ABP), in mainstream cigarette smoke was established. The proposed method was based on two-dimensional online solid phase extraction combined with liquid chromatography tandem mass spectrometry (SPE/LC-MS/MS). The particulate phase of the mainstream cigarette smoke was collected on a Cambridge filter pad and pretreated via ultrasonic extraction with 2% formic acid (FA), while the gas phase was trapped by 2% FA without pretreatment for determination. The two-dimensional online SPE comprised of two cartridges with different absorption characteristics was applied for sample pretreatment. Analysis was performed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) under multiple reaction monitoring mode. Each sample required about 0.5h for solid phase extraction and analysis. The limit of detections (LODs) for six AAs ranged from 0.04 to 0.58ng/cig and recoveries were within 84.5%-122.9%. The relative standard deviations of intra- and inter-day tests for 3R4F reference cigarette were less than 6% and 7%, respectively, while no more than 7% and 8% separately for a type of Virginia cigarette. The proposed method enabled minimum sample pretreatment, full automation, and high throughput with high selectivity, sensitivity, and accuracy. As a part of the validation procedure, fifteen brands of cigarettes were tested by the designed method., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Metal-organic framework (MOF) MIL-100(Fe) with well-defined thickness was homogenously coated onto the outer surface of magnetic microparticles via a liquid-phase epitaxy method. The as-synthesized MIL-100(Fe) was used as stationary phase for high-performance liquid chromatography (HPLC) and separations of two groups of mixed aromatic hydrocarbons (toluene, styrene and p-xylene; acetanilide, 2-nirtoaniline and 1-naphthylamine) using methanol/water as mobile phase were performed to evaluate its performance. Increasing water content of the mobile phase composition can greatly improve the separations on the expense of a longer elution time. Stepwise elution significantly shortens the elution time of acetanilide, 2-nirtoaniline and 1-naphthylamine mixtures, while still achieving a baseline separation. Combining the experimental results and in-depth modeling using a recently developed chromatographic software (ChromX), adsorption equilibrium parameters, including the affinities and maximum capacities, for each analyte toward the MIL-100(Fe) are obtained. In addition, the pore diffusivity of aromatic hydrocarbons within MIL-100(Fe) was determined to be 5×10(-12)m(2)s(-1). While the affinities of MIL-100(Fe) toward the analyte molecules differs much, the maximum capacities of the analytes are in a narrow range with q*MOFmax,toluene=3.55molL(-1), q*MOFmax,styrene or p-xylene=3.53molL(-1), and q*MOFmax,anilines=3.12molL(-1) corresponding to approximately 842 toluene and 838 styrene or p-xylene, and 740 aniline molecules per MIL-100(Fe) unit cell, respectively., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Natural organic matter (NOM) is a complex and non-uniform mixture of organic compounds which plays an important role in environmental processes. Due to the complexity, it is challenging to obtain fully detailed structural information about NOM. Although Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) has been demonstrated to be a powerful tool for providing molecular information about NOM, multiple ionization methods are needed for comprehensive characterization of NOM at the molecular level considering the ionizing selectivity of different ionization methods. This paper reports the first use of matrix assisted laser desorption/ionization (MALDI) method coupled with FT-ICR-MS for molecular characterization of NOM within a mass range of 200-800 Da. The mass spectral data obtained by MALDI were systematically compared with data generated by electrospray ionization (ESI). It showed that complementary molecular information about NOM which could not be detected by ESI, were provided by MALDI. More unsaturated and aromatic constituents of NOM with lower O/C ratio (O/C ratio<0.5) were preferentially ionized in MALDI negative mode, whereas more polar constituents of NOM with higher O/C ratio were preferentially ionized in ESI negative mode. Molecular anions of NOM appearing at even m/z in MALDI negative ion mode were detected. The results show that NOM molecules with aromatic structures, moderate O/C ratio (0.7>O/C ratio>0.25) and lower H/C ratio were liable to form molecular anions at even m/z, whereas those with higher H/C ratio are more likely to form deprotonated ions at odd m/z. It is speculated that almost half of the NOM molecules identified by MALDI may be aromatic or condensed aromatic compounds with special groups which are liable to absorb electron from other molecules to generate free radical anions during MALDI ionization., (Copyright © 2015. Published by Elsevier B.V.)

Urinary aromatic amines (AAs) could be used as biomarkers for human exposure to AAs in cigarette smoke. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the determination of urinary AAs (i.e. 1-naphthylamine (1-NA), 2-naphthylamine (2-NA), 3-aminobiphenyl (3-ABP) and 4-aminobiphenyl (4-ABP)) in smokers and nonsmokers. A molecularly imprinted polymers (MIPs) solid phase extraction (SPE) cartridge was applied to purify urine samples and no derivatization reaction was involved. Each analytes used respective stable isotope internal standards, which could well compensate matrix effect. Lower limit of detections (LODs) for four AAs were obtained and in the range of 1.5-5ngL(-1). Recovery ranged from 87.7±4.5% to 111.3±6.4% and precision were less than 9.9%. The method was applied to analyze urine samples of 40 smokers and 10 nonsmokers. The 24h urinary excretion amounts of total AAs were higher for smokers compared with nonsmokers. What's more, 1-NA, 3-ABP and 4-ABP excretion amounts showed significant differences (p<0.05) between smokers and nonsmokers., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The amino-substituted naphthalene compounds, such as 1,8-diaminonaphthalene (1,8-DANAP), 2,3-diaminonaphthalene (2,3-DANAP), 1,5-diaminonaphthalene (1,5-DANAP), 1-naphthylamine (1-NAP) and 2-naphthylamine (2-NAP), were investigated by electrochemical impedance spectroscopy (EIS), which was based on the interaction with hairpin DNA immobilized on the gold electrodes. Upon hairpin DNA interacting with the target chemicals, the charge transfer resistance (RCT) of the hairpin DNA films was significantly decreased and the charge transfer resistance change (ΔR(CT)) decreased in a sequence of ΔR(CT) (1,8-DANAP)>ΔR(CT) (2,3-DANAP)>ΔR(CT) (1,5-DANAP)>ΔR(CT) (1-NAP)>ΔR(CT) (2-NAP). The ΔR(CT) changes were due to the difference in the binding constant (K(SV)) of the target chemicals to DNA. In addition, the interaction mechanism was further explored using 1,8-DANAP as a model analyte by fluorescence spectra, Raman spectroscopy, differential pulse voltammetry (DPV) and EIS, correspondingly. The results demonstrated that the amino-substituted naphthalene compounds intercalated into "stem" appearing in the hairpin DNA. Moreover, the hairpin DNA sensor exhibited high sensitivity to the amino-substituted naphthalene compounds with the detection limit of nano-mole, and maintained high selectivity over other selected environmental pollutants. Finally, the DNA sensor was challenged in natural water sample with a recovery of 96-102%, which offered a platform for prospective future development of a simple, rapid, sensitive and low-cost assay for the detection of target aromatic amine pollutants., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)

Carbon nanotubes (CNTs) can exist in the form of colloidal suspension in aquatic environments, particularly in the presence of natural organic matter or surfactants, and may significantly affect the fate and transport of organic contaminants. In the present study, the authors examined the adsorption of phenanthrene, 2-naphthol, and 1-naphthylamine to three colloidal CNTs, including a stable suspension of oxidized multiwalled carbon nanotubes (O-MWNT), a humic acid (HA)-modified colloidal O-MWNT, and a sodium dodecyl sulfate (SDS)-modified colloidal O-MWNT. All three colloidal O-MWNTs exhibit strong adsorption affinities to the three test compounds (with K(OC) values orders of magnitude greater than those of natural organic matter), likely resulting from strong nonhydrophobic interactions such as π-π electron donor-acceptor interactions and Lewis acid-base interactions. When thoroughly mixed, HA (at ∼310 mg HA/g CNT) and SDS (at ∼750 mg SDS/g CNT) significantly affected the aggregation properties of O-MWNT, causing individually dispersed tubes to form a loosely entangled network. The effects of HA or SDS modification on adsorption are twofold. Adsorption of HA/SDS significantly reduces surface areas of O-MWNT; however, the entangled network allows adsorbate molecules to interact simultaneously with multiple tubes. An important implication is that humic substances and surfactant-like materials not only facilitate the formation of colloidal carbon nanoparticles but also affect how these colloidal carbon nanoparticles adsorb organic contaminants., (Copyright © 2013 SETAC.)

Sertraline is a commonly prescribed selective inhibitor of serotonin uptake used for the treatment of mental depression and anxiety. Central blood and liver concentrations of sertraline (norsertraline) are compared to levels in peripheral blood in nine medical examiner cases. Specimens were initially screened for alcohol and simple volatiles by GC-FID headspace analysis, ELISA for drugs of abuse, and alkaline drugs by GC/MS. Sertraline, when detected by the alkaline drug screen, was subsequently confirmed and quantified by a specific GC-NPD procedure. Data suggest that when ingested with other medications, sertraline may be a contributing factor in death. Sertraline (norsertraline) concentrations ranged from 0.13 (0.11) to 2.1 (6.0) mg/L in peripheral blood, from 0.18 (0.12) to 2.0 (6.7) mg/L in central blood, and 21 to 160 mg/kg in liver. Sertraline central blood to peripheral blood ratios averaged 1.22±0.85 (mean±standard deviation). The liver to peripheral blood ratios, on the other hand, were markedly higher and averaged 97±40 (mean±standard deviation). Given that a liver to peripheral blood ratio exceeding 20 is indicative of propensity for significant postmortem redistribution, these data confirm that sertraline is prone to marked postmortem redistribution., (Published by Elsevier Ireland Ltd.)

Odorant-binding proteins (OBPs) are found in both insects and vertebrates, and it is believed that they are involved in chemical communication. In this study, we identify and express 2 OBPs from the scarab beetle, Holotrichia oblita Faldermann (Coleoptera: Scarabaeidae). HoblOBP1 shows more similarities with other scarab beetle OBPs, whereas HoblOBP2 is more diverse. N-phenyl-1-naphthylamine (1-NPN) is used as a fluorescent probe in ligand-binding experiment, and results indicate that both HoblOBPs prefer plant volatiles to putative H. oblita sex pheromones. HoblOBP1 shows binding affinity to a wider range of test compounds, but HoblOBP2 displays more specific binding affinity. Cinnamaldehyde and 2,4-di-tert-butylphenol bind to HoblOBP1 can elicit strong electrophysiological responses of the antennae from female H. oblita adults, respectively. Methyl salicylate also shows good affinity to HoblOBP2 and it can elicit moderate electrophysiological responses. Although, β-ionone is one of the ligands of the strongest binding, it elicits a weak electrophysiological response. In the immunocytochemical analysis, we observe that HoblOBP1 and HoblOBP2 are coexpressed in sensilla basiconica and placodea in both sexes.

A method for the determination of 4,4'-methylenedianiline, aniline, o-anisidine, 3, 4-dimethylaniline, p-anisidine, 3-aminophenol, 1-naphthylamine in hair dyes was established by capillary electrophoresis coupled with field-amplified sample stacking. The optimum running buffer was an aqueous solution containing 0.15 mol/L NaH2PO4 and 0.015 mol/L trolamine (pH 2.3), and the baseline separation was achieved within 6.5 min. The effects of phosphoric acid and acetonitrile concentration in the sample matrix, the length of the preinjection water plug, and the sample injection voltage and time on the stacking efficiency were investigated. The optimum stacking conditions for the real samples included a water plug of 3.45 kPa (0.5 psi) x 6 s, the addition of 40% (v/v) acetonitrile and 0.6 x 10(-3) mol/L phosphoric acid to the sample solution and a sample injection of 10 kV x 10 s. The seven analytes all showed good linearities (R2 > 0.996) within 3 - 1 000 microg/L, with the detection limits in the range of 0.26 - 2.75 microg/L. The method was shown to provide over 1 - 3 magnitudes of sensitivity enhancement. 3-Aminophenol was found in two black hair dyes, and the amounts were 7.32 mg/g and 1.34 mg/g, individually. The recoveries ranged from 74% - 108%. The proposed approach may find widespread applications for the determination of trace aromatic amines and other cationic analytes in various sample matrixes.

The first polyurethane based magnetic-MIP for the selective detection of 1-naphthylamine (1-NA) in drinking water has been synthesised. The synthesis has been carried out in a two-step process: first,the incorporation of magnetite-coated-oleic acid nanoparticles (-Fe₃O₄-OA) into a lipophilic polymeric matrix (poly-MMA-co-EDMA) and second, the encapsulation of these magnetic seeds into the MIP structure by precipitation polymerisation. The mag-MIP was first RHTEM imaged showing a well-organised material with magnetite within the material and the imprinted polymer coating the magnetic core. Thereafter,it was evaluated by batch rebinding analysis and the derived Freundlich isotherm, calculating the number of binding sites (N(K(min)-K(max))=2.63 and 0.79 mmol g⁻¹, for mag-MIP and mag-NIP, respectively)and apparent average adsorption constant (K(K(min)-K(max))=3.31 and 3.06 mmol⁻¹, for mag-MIP and mag-NIP, respectively) showing a very effective imprinting process.We have also developed a magnetic optical sensor MIP by using an optical fiber coupled with a magnetic separator. An unexpected selectivity for 1-NA was revealed allowing the detection of this molecule in water, even in the presence of 4 structurally related compounds (2-naphthylamine, 1-naphthol, 2-naphthol and 1-naphthalenemethylamine), with a low limit of detection (LOD) = 18 ng mL⁻¹. Finally, we applied this new hybrid material to the analysis of 1-NA in tap and mineral waters, obtaining a 91.6%average recovery rate., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Enantiomeric amphipathic α-helical antibacterial peptides were synthesized and their biophysical and biological properties under different physiological conditions were studied. In the absence of physiological factors, the L- and D-peptides exhibited similar antimicrobial activities against a broad spectrum of bacteria, even against clinical isolates with resistance to traditional antibiotics. However, in the presence of NaCl, CaCl₂ or human serum albumin (HSA) at physiological concentrations, the enantiomers revealed bacterium-species dependent attenuations in antibacterial activity. In the presence of salts the electrostatic interaction between the peptides and the biomembrane was inhibited. Salts, especially CaCl₂ weakened the ability of the peptides to permeabilize the outer membrane of Gram-negative bacteria, as determined by a 1-N-phenylnaphthylamine uptake assay. HSA exhibited variable inhibitory effects on the activity of the peptides when incubated with different bacterial strains. The peptides showed different binding association abilities to HSA at different molar ratios, regardless of their chirality, resulting in reduced peptide biological activity. The D-peptide performed better than its L-enantiomer in all conditions tested because of its resistance to proteolysis, and may therefore represent a promising candidate for development as a therapeutic agent., (Copyright © 2011 Elsevier Inc. All rights reserved.)

We estimated pollution in Lake Edku and the Mediterranean Sea, El-Maadiya Region, with 3 aromatic amines (1-naphthylamine, 2-naphthylamine and benzidine) in the muscle tissue of fish. There were marked seasonal variations in the aromatic amine levels. We also determined oxidative stress (blood glutathione, and catalase activity) and genotoxic effects (chromosomal aberrations and urinary metabolites) in fishermen from each area. The fishermen suffered from oxidative stress and had high levels of the urinary metabolite sulfanilamide [mean (microg/mg creatinine): Lake Edku 20.7, Mediterranean 14.5, controls 5.3]. Frequencies for total chromosomal aberrations were significantly raised in the peripheral blood lymphocytes of fishermen in both areas [frequency (per 100 metaphases): Mediterranean 67, Lake Edku 45, controls 14].

A simple and rapid analytical method for determining 1-naphthylamine was proposed by perturbation with different amounts of 1-naphthylamine on the classical Belousov-Zhabotinskii (B-Z) oscillating chemical system. The results show that the changes both in oscillating period and amplitude were linearly proportional to the logarithm of the concentration of 1-naphthylamine (logC) very well ranging from 7.08x10(-5) to 7.08x10(-6) molL(-1) and 7.08x10(-5) to 1.0x10(-6) molL(-1), with the corresponding regression coefficient are 0.9957 and 0.9922, respectively. For the later, a lower detection limit of 5.64x10(-9) molL(-1) was obtained. Influence of injection point, temperature and reactant variables on this oscillating system was also investigated in detailed. The results obtained were compared with other determination methods. A possible reaction mechanism was interpreted by using bromide ion selective electrode to inspect the concentration change of Br(-) ion in the oscillating process.

Metabonomics using high-resolution 1H-NMR spectroscopy of biofluids and pattern recognition is highly successful at distinguishing both organ- and sub-organ-specific toxicity. In the current study, this technique was investigated to distinguish the different biological effects caused by 1-naphthylisothiocyanate (ANIT)-induced hepatotoxicity in the rat from that induced by exposure to 1-naphthylisocyanate (NI) and 1-naphthylamine (NA), two products of the metabolism of ANIT. While all three toxicants produced perturbations in similar urinary metabolites, principal components analysis of the temporal progression identified that the rapid initial glycosuria associated with ANIT toxicity was also present with NI but not NA dosing. However, longer-term perturbations in the urinary excretion of succinate, lactate and acetate were common to all three toxicants. The metabolic effects of the three compounds were also followed in blood plasma and liver tissue. Of the three toxicants, the most marked perturbations were induced by ANIT exposure, then NI, thereby indicating the effects of ANIT, NI and NA toxicity were distinct, with ANIT being the most, and NA the least, toxic of the three compounds. This indicates that metabonomics may be useful for following severity and mechanisms of toxicity in a series of related compounds during drug development.

In this paper, an internal conversion (IC) fluorescence probe N-(o-boronic acid)benzyl-1-naphthylamine (BBNA) was prepared from 1-naphthylamine and 2-formylbenzeneboronic acid. The fluorescence parameters of BBNA were investigated in a variety of solvents. When BBNA interacted with D-fructose in phosphate buffer solution of 30% MeOH, pH 8.21 (v/v), the fluorescence intensity increased and emission maximum red-shifted slightly with increasing D-fructose concentration. In the presence of D-fructose, the fluorescence quantum yield of BBNA increased with increasing solvent polarity, suggesting that internal conversion (IC) occurred with BBNA. The binding force of BBNA with d-fructose was the strongest, and the stability constant (K) of D-fructose was 99.9 mol/L. Therefore, a selective recognition system based on IC was constructed for D-fructose., (Copyright 2005 John Wiley & Sons, Ltd.)

Essential oils from Artemisia annul L. were extracted with CO2 supercritical fluid and steam distilation. The essential oils were analyzed and contrasted by GC-MS. 114 components were identified by computer index. The rate of total components by supercritical CO2 fluid extraction and steam distillation were 81.24% and 85.75% respectively. Some of them such as diphenylene-Methane, Phenyl-1-naphthylamine were discovered from the plant for the first time.

A gas chromatography-mass spectrometry method is presented which allows the simultaneous determination of the plasma concentrations of the selective serotonin reuptake inhibitors citalopram, paroxetine, sertraline, and their pharmacologically active N-demethylated metabolites (desmethylcitalopram, didesmethylcitalopram, and desmethylsertraline) after derivatization with the reagent N-methyl-bis(trifluoroacetamide). No interferences from endogenous compounds are observed following the extraction of plasma samples from six different human subjects. The standard curves are linear over a working range of 10-500 ng/mL for citalopram, 10-300 ng/mL for desmethylcitalopram, 5-60 ng/mL for didesmethylcitalopram, 20-400 ng/mL for sertraline and desmethylsertraline, and 10-200 ng/mL for paroxetine. Recoveries measured at three concentrations range from 81 to 118% for the tertiary amines (citalopram and the internal standard methylmaprotiline), 73 to 95% for the secondary amines (desmethylcitalopram, paroxetine and sertraline), and 39 to 66% for the primary amines (didesmethylcitalopram and desmethylsertraline). Intra- and interday coefficients of variation determined at three concentrations range from 3 to 11% for citalopram and its metabolites, 4 to 15% for paroxetine, and 5 to 13% for sertraline and desmethylsertraline. The limits of quantitation of the method are 2 ng/mL for citalopram and paroxetine, 1 ng/mL for sertraline, and 0.5 ng/mL for desmethylcitalopram, didesmethylcitalopram, and desmethylsertraline. No interferences are noted from 20 other psychotropic drugs. This sensitive and specific method can be used for single-dose pharmacokinetics. It is also useful for therapeutic drug monitoring of these three drugs and could possibly be adapted for the quantitation of the two other selective serotonin reuptake inhibitors on the market, namely fluoxetine and fluvoxamine.

Aims: To characterise milk/plasma (M/P) ratio and infant exposure, for sertraline and N-desmethylsertraline, in breast-feeding women taking sertraline for the treatment of depression., Methods: Eight women (mean age 28 years) taking sertraline (1.05 mg kg(-1) day(-1)) and their infants (mean age 5.7 months) were studied. Sertraline and N-desmethylsertraline in plasma and milk were measured by high-performance liquid chromatography over a 24 h dose interval at steady-state. M/P values were estimated from area under the plasma and milk concentration-time curves. All milk produced was collected over the dose interval. Infant exposure was estimated as the product of actual or estimated milk production, and average drug concentration in milk, normalized to body weight and expressed as a percentage of the weight-adjusted maternal dose., Results: Mean milk production was 321 ml day(-1) (range 34-974 ml). Mean M/P values of 1.93 and 1.64 were calculated for sertraline and N-desmethylsertraline respectively. Infant exposure estimated from actual milk produced was 0.2% and 0.3% of the weight-adjusted maternal dose for sertraline and N-desmethylsertraline (as sertraline equivalents) respectively. When calculated from estimated milk production (0.15 l kg(-1) day(-1)), infant exposure was significantly greater (P<0.0001) at 0.90% and 1.32% for sertraline and N-desmethylsertraline respectively. Neither sertraline nor its N-desmethyl metabolite could be detected in plasma samples from the four infants tested. No adverse effects were observed in any of the eight infants and all had achieved normal developmental milestones., Conclusions: Irrespective of the method of calculation of infant exposure, the mean total dose of sertraline and its N-desmethyl metabolite transmitted to infants via breast-feeding is low and unlikely to cause any significant adverse effects.

Objective: The purpose of this study was to determine the concentrations of sertraline and desmethylsertraline in both human breast milk and infant serum., Method: Breast milk samples from 12 women were collected at specific time intervals after oral doses of sertraline (25-200 mg once daily). For 11 mother-infant pairs, maternal serum levels 24 hours after a dose and their infants' serum levels 2-4 hours after nursing were ascertained by high-performance liquid chromatography., Results: Sertraline and desmethylsertraline were present in all breast milk samples, with a gradient from "fore" milk to "hind" milk. The highest concentrations of sertraline were observed in hind milk 7-10 hours after maternal dose. Increasing the maternal dose of sertraline resulted in increased breast milk concentrations of both sertraline and desmethylsertraline. Detectable concentrations of sertraline were found in three nursing infants and desmethylsertraline in six. No adverse effects of exposure were observed in any infant., Conclusions: Sertraline and desmethylsertraline were present in the breast milk of nursing women treated with sertraline. Concentrations were affected by aliquot of milk sampled, time after maternal dose, and maternal daily dose. The infants' serum concentrations detected were below the detection limit of most commercial laboratories. The presence of desmethylsertraline in six infants' samples underscores the importance of metabolite monitoring in determining infant exposure. Estimates of daily infant exposure can be determined after analysis of sertraline and desmethylsertraline concentrations from one full breast at maternal serum steady state. Future studies of breast milk and infant serum samples should address these issues.

Background: In assessing the safety of medication use in breastfeeding, it is important to know whether the drug used by the mother will be present in the breastfed infant. Compared with data for tricyclic antidepressants (TCAs), which have generally not been found in the plasma of breastfed infants, there are few data on the use of serotonin selective reuptake inhibitors (SSRIs) in breastfeeding. This poses a dilemma for breastfeeding women and their treating clinicians, because of the enhanced tolerability of SSRIs compared with TCAs, and because some patients do not respond well to TCAs., Method: Sertraline and norsertraline plasma concentrations were measured in three breastfeeding mother-infant pairs. Maternal and infant plasma samples were drawn a few minutes apart. Two of the infants had an additional sample assayed without contemporaneous maternal samples examined. Drug assay was by high-performance liquid chromatography. Limit of reproducible quantifiability was 2 ng/mL, and limit of detectability was 1 ng/mL., Results: Maternal sertraline dose ranged from 50 to 100 mg/day. All infant plasma samples showed low levels (< 2 ng/mL) of either sertraline and norsertraline or norsertraline alone. Breastfeeding was continued, and the infants have shown no adverse effects on short-term follow-up., Conclusion: These data suggest that sertraline and/or its almost inactive metabolite may be present at very low concentrations in the plasma of breastfed infants. No adverse effects were noted in the infants. Limitations of the findings and possible implications for the use of sertraline during breastfeeding are discussed.

Initial experiments demonstrated that the original CEDIA (cloned enzyme donor immunoassay) benzodiazepine assay crossreacted with setraline and sertraline metabolites. In response to this phenomenon, Boehringer Mannheim Corporation developed an improved CEDIA benzodiazepine assay in order to eliminate sertraline crossreactivity. The improved CEDIA assay was evaluated against the original CEDIA product, EMIT II (enzyme multiplied immunoassay technique) benzodiazepine assay, and electron capture negative chemical ionization (ECNCI) gas chromatography-mass spectrometry (GC-MS). Five hundred and thirty-one urine drug screens were tested by the immunoassays. Sensitivity and specificity of these immunoassays for the 5-aryl-7-chloro-1,4-benzodiazepine compounds were 92 and 98%, respectively, for the improved CEDIA assay; 92 and 93%, respectively, for the current CEDIA assay; and 87 and 98%, respectively, for EMIT II. The improved CEDIA assay performed almost identically to the EMIT II assay, both of which had a significant advantage over the original CEDIA product, which was subject to crossreactivity because of sertraline metabolites. The alpha-hydroxy ketone metabolites of sertraline are identified in human urine specimens for the first time using ECNCI GC-MS.

Five selective serotonin reuptake inhibitors (SSRIs) have been introduced recently: citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline. Although no therapeutic window has been defined for SSRIs, in contrast to tricyclic antidepressants, analytical methods for therapeutic drug monitoring of SSRIs are useful in several instances. SSRIs differ widely in their chemical structure and in their metabolism. The fact that some of them have N-demethylated metabolites, which are also SSRIs, requires that methods be available which allow therapeutic drug monitoring of the parent compounds and of these active metabolites. most procedures are based on prepurification of the SSRIs by liquid-liquid extraction before they are submitted to separation by chromatographic procedures (high-performance liquid chromatography, gas chromatography, thin layer chromatography) and detection by various detectors (UV, fluorescence, electrochemical detector, nitrogen-phosphorus detector, mass spectrometry). This literature review shows that most methods allow quantitative determination of SSRIs in plasma, in the lower ng/ml range, and that they are, therefore, suitable for therapeutic drug monitoring purposes of this category of drugs.

Background: Few reports exist on the levels of antidepressants in breast milk or on observed behavioral effects, if any, of neonates who are breast-fed. Thus, a dilemma exists for women who would like to breast-feed but require psychotropic medications., Method: Analysis of sertraline levels was performed on eight samples of breast milk obtained over a 24-hour period, after 3 weeks of breastfeeding, from a lactating patient taking sertraline and nortriptyline. During this same 24-hour period, two serum samples each were taken from mother and child for analysis of sertraline and nortriptyline levels. After 7 weeks of exclusive breastfeeding, an additional serum sample was obtained from mother and child for analysis of sertraline levels. Drug metabolites were not measured., Results: Breast milk levels of sertraline were lowest 1 hour before the ingestion of sertraline and highest 5 to 9 hours after ingestion of the drug. The infant's serum sertraline and nortriptyline levels were nondetectable., Conclusion: These data indicate that sertraline levels in breast milk vary substantially over 24 hours and appear to be lowest within the 2 hours before and 1 hour after ingestion of the medication, with the peak probably occurring between Hours 1 and 9 postingestion. However, the absence of detectable serum sertraline and nortriptyline levels in the infant suggests that if either medication is present in infant serum, its concentration would be extremely low. No abnormal occurrences have been noted in the development of the infant. It would be important in future studies to measure metabolites in addition to medication levels since the former have been associated with untoward events in an infant.

Sertraline is a potent inhibitor of serotonin reuptake in the central nervous system and is used clinically to treat depression and obsessive-compulsive behavior. Over the course of one year, there were seven cases investigated by the Office of the Chief Medical Examiner, State of Maryland, in which sertraline was identified in postmortem specimens. Heart blood concentrations in the seven cases ranged from 0.23 to 0.46 mg/L; desmethylsertraline concentrations ranged from 0.08 to 0.99 mg/L. One similarity with tricyclic antidepressants is the high liver concentrations of drug and metabolite relative to the blood. One unusual finding is the small concentrations of drug and metabolite in the urine relative to other specimens. In none of these cases was the cause of death related to sertraline intoxication.

We report methods for the analysis of sertraline and desmethylsertraline in postmortem biological fluids. The extraction method is based on a widely used procedure employing n-butyl chloride, and instrumental analysis is performed using GC/MS and HPLC with photodiode array detection. We report retention index, mass spectral, and UV-vis properties of the drug and its metabolite. Samples from three sertraline-related deaths were analyzed and revealed concentrations up to 10 times greater than the normal therapeutic levels, although two of the deaths were obviously the result of other causes. We also noted in one case that the drug concentrations in central and peripheral blood were very similar, suggesting that postmortem distribution may be uniform.

The determination of the new antidepressant drug sertraline and its main metabolite, desmethylsertraline, in human serum is described. A new solid-phase extraction method employing the dual functionality Clean Screen cartridge is presented followed by reversed-phase liquid chromatographic (LC) analysis. The sample preparation yielded extremely clean extracts and absolute recoveries in excess of 90% for both drugs from human serum. The response of the LC system was linear over the concentration range 0.01-2.5 mg/l for both sertraline and desmethylsertraline with a limit of detection of 0.01 mg/l. A gas chromatographic-mass spectrometric (GC-MS) system is also described should confirmation of the drugs be necessary.

A method is described for the simultaneous quantitation of trace amounts of alpha- (alpha-NA) and beta-naphthylamines (beta-NA) with detectability in the 0.1 ppb range and sensitivity of 50 picomoles in certified food grade amaranth (FD&C Red No. 2; C.I. Food Red 9; CI 16185). The amaranth sample is extracted with benzene, and the evoporated residue is derivatized with perfluorooctanoic anhydride. The resulting derivatives are separated by gas-liquid chromatography and identified and quantitated by mass spectrometric monitoring of the m/e at 539.04. The method was used for quantitation of alpha-NA and beta-NA in randomly chosen samples of amaranth. Of 11 samples from different manufacturers, 5 were free of the beta-isomer; the remaining samples contained up to 1.2 ppb beta-NA. The concentration of alpha-NA ranged from no detectable amount to 970 ppb; the majority of the samples contained less than 7 ppb.

A new method is described for the determination of the herbicide naptalam and its metabolite 1-naphthylamine in several foods. The method is sensitive, selective, and extremely rapid compared with previously reported methods. Liquid chromatography with electrochemical detection (LC/ECD) is used to determine 1-naphthylamine produced from the metabolism or base hydrolysis of naptalam in asparagus, peaches, and cranberries. These foods were spiked with naptalam at 0.05 and 0.11 ppm and hydrolyzed with 30% NaOH with concomitant distillation of 1-naphthylamine. Aliquots of the distillate were injected onto a reverse-phase PRP-1 LC column for separation of 1-naphthylamine from coextractives near the solvent front and detection at an applied potential of +0.83 V using an amperometric electrochemical detector in the oxidation mode. Recoveries ranged from 89% +/- 2% to 97% +/- 8% for all foods at both spiking levels. Accuracy of these recoveries was confirmed by use of 14C-radiolabeled naptalam and radioassay by liquid scintillation spectrometry of the 14C-1-naphthylamine released.

Circular dichroism curves have been measured for phthaloyl-, maleyl- and itaconyl-derivatives of a number of amines having a general formula R--CH(NH2)--R' (in which R and R' are alkyl-, aryl- or cyclohexyl-groups) and of 1,2,3,4-tetrahydro-1-naphthylamine and 1,2,3,4-tetrahydro-2-naphthylamine. We conclude that the determination of absolute configuration of amines examined can be made on the basis of C.D. curves of their phthaloyl-, maleyl- and itaconyl-derivatives, referring to that portion of the curve relating to the imide chromophore absorption.

The fluorescence of the lipophilic probe N-phenyl-1-naphthylamine (NPN) bound to intact cells of Escherichia coli is quenched by the addition of glucose, succinate, D-lactate, pyruvate, formate and glycerol. Partial recovery of fluorescence occurs on anaerobiosis. Use of mutants with defects in the ATP synthase or the respiratory chain show that quenching of fluorescence may be energized either by ATP hydrolysis or by substrate oxidation through the respiratory chain. Permeabilization of the outer membrane by treatment of intact cells with EDTA, or use of a mutant with an outer membrane permeable to lipophilic substances, results in a more rapid binding of NPN and in a decrease in quenching observed on substrate addition. NPN binds rapidly to everted membrane vesicles, but does not respond to membrane energization. It is proposed that inner membrane energization in intact cells alters the binding or environment of NPN in the outer membrane. The fluorescence recovery which occurs on anaerobiosis has two components. One component represents a reversal of the changes which occur on membrane energization. The other component of the fluorescence change is insensitive to the uncoupler CCCP and resembles the behaviour of NPN with everted membrane vesicles. It is suggested that a portion of the fluorescence events seen with NPN involves a response of the probe to changes in the inner membrane.