An Overview of Degradation Strategies for Amitriptyline.

Antidepressant drugs play a crucial role in the treatment of mental health disorders, but their efficacy and safety can be compromised by drug degradation. Recent reports point to several drugs found in concentrations ranging from the limit of detection (LOD) to hundreds of ng/L in wastewater plants around the globe; hence, antidepressants can be considered emerging pollutants with potential consequences for human health and wellbeing. Understanding and implementing effective degradation strategies are essential not only to ensure the stability and potency of these medications but also for their safe disposal in line with current environment remediation goals. This review provides an overview of degradation pathways for amitriptyline, a typical tricyclic antidepressant drug, by exploring chemical routes such as oxidation, hydrolysis, and photodegradation. Connex issues such as stability-enhancing approaches through formulation and packaging considerations, regulatory guidelines, and quality control measures are also briefly noted. Specific case studies of amitriptyline degradation pathways forecast the future perspectives and challenges in this field, helping researchers and pharmaceutical manufacturers to provide guidelines for the most effective degradation pathways employed for minimal environmental impact.

Development of Visible Spectrophotometric Methods for the Determination of Tricyclic Antidepressants Based on Formation of Molecular Complexes with p-Benzoquinones.

Tricyclic antidepressants are commonly employed in the management of major depressive disorders. The present work describes two visible (VIS) spectrophotometric techniques that utilize the formation of charge transfer complexes between four antidepressant compounds, namely, amitriptyline hydrochloride (AMI), imipramine hydrochloride (IMI), clomipramine hydrochloride (CLO), and trimipramine maleate (TRI) acting as electron donors and two p-benzoquinones, namely, p-chloranilic acid (pCA) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), serving as electron acceptors. The stoichiometry of the compounds produced exhibited a consistent 1:1 ratio in all instances, as established by Job's method. Molar absorptivities, equilibrium association constants, and several other spectroscopic properties were determined for all complexes. The developed spectrophotometric techniques were validated intra-laboratory and successfully applied for quantitative assessment of the four antidepressant active ingredients in several commercial pharmaceutical formulations. The methods are relatively simple, fast, and use readily available laboratory instrumentation, making them easily applicable by most quality control laboratories worldwide.

Microemulsions of Nonionic Surfactant with Water and Various Homologous Esters: Preparation, Phase Transitions, Physical Property Measurements, and Application for Extraction of Tricyclic Antidepressant Drugs from Aqueous Media.

Microemulsions are nanocolloidal systems composed of water, an oil, and a surfactant, sometimes with an additional co-surfactant, which have found a wide range of practical applications, including the extractive removal of contaminants from polluted water. In this study, microemulsion systems, including a nonionic surfactant (Brij 30), water, and esters selected from two homologous series of C1-C6 alkyl acetates and ethyl C1-C4 carboxylates, respectively, were prepared by the surfactant titration method. Phase transitions leading to the formation of Winsor II and Winsor IV microemulsions were observed and phase diagrams were constructed. The dependences of phase transitions on the salinity and pH and the addition of isopropanol as a co-surfactant were also investigated. Some physical properties, namely density, refractive index, electrical conductivity, dynamic viscosity, and particle size, were measured for a selection of Winsor IV microemulsions, providing further insight into some other phase transitions occurring in the monophasic domains of phase diagrams. Finally, Winsor II microemulsions were tested as extraction solvents for the removal of four tricyclic antidepressant drugs from aqueous media. Propyl acetate/Brij 30/H2O microemulsions provided the best extraction yields (>90%), the highest Nernst distribution coefficients (~40-88), and a large volumetric ratio of almost 3 between the recovered purified water and the resulting microemulsion extract. Increasing the ionic strength (salinity) or the pH of the aqueous antidepressant solutions led to an improvement in extraction efficiencies, approaching 100%. These results could be extrapolated to other classes of pharmaceutical contaminants and suggest ester- and nonionic surfactant-based microemulsions are a promising tool for environmental remediation.

Curcumin: Overview of Extraction Methods, Health Benefits, and Encapsulation and Delivery Using Microemulsions and Nanoemulsions.

Curcumin is the principal curcuminoid found in the rhizomes of turmeric. Due to its therapeutic action against cancer, depression, diabetes, some bacteria, and oxidative stress, it has been used widely in medicine since ancient times. Due to its low solubility, the human organism cannot completely absorb it. Advanced extraction technologies, followed by encapsulation in microemulsion and nanoemulsion systems, are currently being used to improve bioavailability. This review discusses the different methods available for curcumin extraction from plant material, methods for the identification of curcumin in the resulting extracts, its beneficial effects on human health, and the encapsulation techniques into small colloidal systems that have been used over the past decade to deliver this compound.

Effects of Smoking Temperature, Smoking Time, and Type of Wood Sawdust on Polycyclic Aromatic Hydrocarbon Accumulation Levels in Directly Smoked Pork Sausages.

Smoking is an excellent food preservation method but also a source of contamination of foodstuffs with carcinogenic polycyclic aromatic hydrocarbons (PAHs). Herein we investigated the influence of smoking temperature, smoking time, and type of wood sawdust used as smoke source on PAH levels attained through controlled smoking of pork sausages. Four PAHs (benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[a]pyrene) were monitored, as required by European Commission Regulation 835/2011. PAH concentrations increased continuously both with higher temperatures (55-95 °C) and with longer smoking periods (2-9 h), although the level of benzo[a]pyrene exhibited a tendency to plateau after 6 h. Among seven types of hardwoods tested, plum, alder, and birch yielded PAH concentrations considerably higher than that of commonly used beech, and oak showed similar levels to beech while apple and, to a lesser extent, walnut caused lower levels of sausage contamination. These findings could guide the establishment of good practices in the smoked meat industry.

A Novel Multifunctional C-23 Oxidase, CYP714E19, is Involved in Asiaticoside Biosynthesis.

Centella asiatica is widely used as a medicinal plant due to accumulation of the ursane-type triterpene saponins asiaticoside and madecassoside. The molecular structure of both compounds suggests that they are biosynthesized from α-amyrin via three hydroxylations, and the respective Cyt P450-dependent monooxygenases (P450 enzymes) oxidizing the C-28 and C-2α positions have been reported. However, a third enzyme hydroxylating C-23 remained elusive. We previously identified 40,064 unique sequences in the transcriptome of C. asiatica elicited by methyl jasmonate, and among them we have now found 149 unigenes encoding putative P450 enzymes. In this set, 23 full-length cDNAs were recognized, 13 of which belonged to P450 subfamilies previously implicated in secondary metabolism. Four of these genes were highly expressed in response to jasmonate treatment, especially in leaves, in accordance with the accumulation patterns of asiaticoside. The functions of these candidate genes were tested using heterologous expression in yeast cells. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that yeast expressing only the oxidosqualene synthase CaDDS produced the asiaticoside precursor α-amyrin (along with its isomer ß-amyrin), while yeast co-expressing CaDDS and CYP716A83 also contained ursolic acid along with oleanolic acid. This P450 enzyme thus acts as a multifunctional triterpenoid C-28 oxidase converting amyrins into corresponding triterpenoid acids. Finally, yeast strains co-expressing CaDDS, CYP716A83 and CYP714E19 produced hederagenin and 23-hydroxyursolic acid, showing that CYP714E19 is a multifunctional triterpenoid oxidase catalyzing the C-23 hydroxylation of oleanolic acid and ursolic acid. Overall, our results demonstrate that CaDDS, CYP716A83 and CYP714E19 are C. asiatica enzymes catalyzing consecutive steps in asiaticoside biosynthesis.

Identification of Polyketides in the Cuticular Waxes of Triticum aestivum cv. Bethlehem.

Cuticular waxes are complex mixtures consisting mostly of very-long-chain aliphatics with single, primary functional groups. However, the waxes of many plant species also include aliphatics with one or more functional groups residing on subterminal or mid-chain carbons. In the present work, the cuticular wax mixtures from flag leaf blades and peduncles of Triticum aestivum cv. Bethlehem were analyzed in a search for novel wax constituents with in-chain functionalities, potentially of polyketide origin. The structures of compounds belonging to six different compound classes were elucidated using gas chromatography-mass spectrometry of various derivatives. Among them, a series of 2,4-ketols was identified, with odd carbon numbers ranging from C25 to C37 and peaking at C33. The analogous C33 2,4-diketone was identified as well, together with a pair of co-eluting C31 mid-chain ß-ketol isomers (16-hydroxyhentriacontan-14-one and 14-hydroxyhentriacontan-16-one), a pair of co-eluting C30 mid-chain α-ketol isomers (15-hydroxytriacontan-14-one and 14-hydroxytriacontan-15-one), the corresponding C30 14,15-diketone, and a pair of co-eluting C31 ketones (hentriacontan-14-one and hentriacontan-16-one). All newly discovered structures contain ketone functional groups, with similar C13H27 and C15H31 alkyl chains on either side of the functionalities, thus resembling the previously reported very-long-chain ß-diketones dominating the wheat wax mixtures. Based on these structural characteristics, possible biosynthetic pathways leading to the newly identified polyketide-like compounds are proposed.

Identification of In-Chain-Functionalized Compounds and Methyl-Branched Alkanes in Cuticular Waxes of Triticum aestivum cv. Bethlehem.

In this work, cuticular waxes from flag leaf blades and peduncles of Triticum aestivum cv. Bethlehem were investigated in search for novel wax compounds. Seven wax compound classes were detected that had previously not been reported, and their structures were elucidated using gas chromatography-mass spectrometry of various derivatives. Six of the classes were identified as series of homologs differing by two methylene units, while the seventh was a homologous series with homologs with single methylene unit differences. In the waxes of flag leaf blades, secondary alcohols (predominantly C27 and C33), primary/secondary diols (predominantly C28) and esters of primary/secondary diols (predominantly C50, combining C28 diol with C22 acid) were found, all sharing similar secondary hydroxyl group positions at and around C-12 or ω-12. 7- and 8-hydroxy-2-alkanol esters (predominantly C35), 7- and 8-oxo-2-alkanol esters (predominantly C35), and 4-alkylbutan-4-olides (predominantly C28) were found both in flag leaf and peduncle wax mixtures. Finally, a series of even- and odd-numbered alkane homologs was identified in both leaf and peduncle waxes, with an internal methyl branch preferentially on C-11 and C-13 of homologs with even total carbon number and on C-12 of odd-numbered homologs. Biosynthetic pathways are suggested for all compounds, based on common structural features and matching chain length profiles with other wheat wax compound classes.

Composition of the epicuticular waxes coating the adaxial side of Phyllostachys aurea leaves: Identification of very-long-chain primary amides.

The present study presents comprehensive chemical analyses of cuticular wax mixtures of the bamboo Phyllostachys aurea. The epicuticular and intracuticular waxes were sampled selectively from the adaxial side of leaves on young and old plants and investigated by gas chromatography-mass spectrometry and flame ionization detection. The epi- and intracuticular layers on young and old leaves had wax loads ranging from 1.7 µg/cm(2) to 1.9 µg/cm(2). Typical very-long-chain aliphatic wax constituents were found with characteristic chain length patterns, including alkyl esters (primarily C48), alkanes (primarily C29), fatty acids (primarily C28 and C16), primary alcohols (primarily C28) and aldehydes (primarily C30). Alicyclic wax components were identified as tocopherols and triterpenoids, including substantial amounts of triterpenoid esters. Alkyl esters, alkanes, fatty acids and aldehydes were found in greater amounts in the epicuticular layer, while primary alcohols and most terpenoids accumulated more in the intracuticular wax. Alkyl esters occurred as mixtures of metamers, combining C20 alcohol with various acids into shorter ester homologs (C36C40), and a wide range of alcohols with C22 and C24 acids into longer esters (C42C52). Primary amides were identified, with a characteristic chain length profile peaking at C30. The amides were present exclusively in the epicuticular layer and thus at or near the surface, where they may affect plant-herbivore or plant-pathogen interactions.

Composition of cuticular waxes coating flag leaf blades and peduncles of Triticum aestivum cv. Bethlehem.

The work herein presents comprehensive analyses of the cuticular wax mixtures covering the flag leaf blade and peduncle of bread wheat (Triticum aestivum) cv. Bethlehem. Overall, Gas Chromatography-Mass Spectrometry and Flame Ionization Detection revealed a wax coverage of flag leaf blades (16 µg/cm(2)) a third that of peduncles (49 µg/cm(2)). Flag leaf blade wax was dominated by 1-alkanols, while peduncle wax contained primarily ß-diketone and hydroxy-ß-diketones, thus suggesting differential regulation of the acyl reduction and ß-diketone biosynthetic pathways in the two analyzed organs. The characteristic chain length distributions of the various wax compound classes are discussed in light of their individual biosynthetic pathways and biosynthetic relationships between classes. Along with previously reported wheat wax compound classes (fatty acids, 1-alkanols, 1-alkanol esters, aldehydes, alkanes, ß-diketone, hydroxy-ß-diketones, alkylresorcinols and methyl alkylresorcinols), esters of 2-alkanols and three types of aromatic esters (benzyl, phenethyl and p-hydroxyphenethyl) are also reported. In particular, 2-heptanol esters were identified. Detailed analyses of the isomer distributions within 1-alkanol and 2-alkanol ester homologs revealed distinct patterns of esterified acids and alcohols, suggesting several wax ester synthases with very different substrate preferences in both wheat organs. Terpenoids, including two terpenoid esters, were present only in peduncle wax.

A Metabolic Gene Cluster in the Wheat W1 and the Barley Cer-cqu Loci Determines ß-Diketone Biosynthesis and Glaucousness.

The glaucous appearance of wheat (Triticum aestivum) and barley (Hordeum vulgare) plants, that is the light bluish-gray look of flag leaf, stem, and spike surfaces, results from deposition of cuticular ß-diketone wax on their surfaces; this phenotype is associated with high yield, especially under drought conditions. Despite extensive genetic and biochemical characterization, the molecular genetic basis underlying the biosynthesis of ß-diketones remains unclear. Here, we discovered that the wheat W1 locus contains a metabolic gene cluster mediating ß-diketone biosynthesis. The cluster comprises genes encoding proteins of several families including type-III polyketide synthases, hydrolases, and cytochrome P450s related to known fatty acid hydroxylases. The cluster region was identified in both genetic and physical maps of glaucous and glossy tetraploid wheat, demonstrating entirely different haplotypes in these accessions. Complementary evidence obtained through gene silencing in planta and heterologous expression in bacteria supports a model for a ß-diketone biosynthesis pathway involving members of these three protein families. Mutations in homologous genes were identified in the barley eceriferum mutants defective in ß-diketone biosynthesis, demonstrating a gene cluster also in the ß-diketone biosynthesis Cer-cqu locus in barley. Hence, our findings open new opportunities to breed major cereal crops for surface features that impact yield and stress response.

Very-long-chain 3-hydroxy fatty acids, 3-hydroxy fatty acid methyl esters and 2-alkanols from cuticular waxes of Aloe arborescens leaves.

The present work aimed at a comprehensive chemical characterization of the cuticular wax mixtures covering leaves of the monocot species Aloe arborescens. The wax mixtures were found to contain typical aliphatic compound classes in characteristic chain length distributions, including alkanes (predominantly C31), primary alcohols (predominantly C28), aldehydes (predominantly C32), fatty acid methyl esters (predominantly C28) and fatty acids (bimodal distribution around C32 and C28). Alkyl esters ranging from C42 to C52 were identified, and found to mainly contain C28 alcohol linked to C16-C20 acids. Three other homologous series were identified as 3-hydroxy fatty acids (predominantly C28), their methyl esters (predominantly C28), and 2-alkanols (predominantly C31). Based on structural similarities and homolog distributions, the biosynthetic pathways leading to these novel wax constituents can be hypothesized. Further detailed analyses showed that the A. arborescens leaf was covered with 15 µg/cm(2) wax on its adaxial side and 36 µg/cm(2) on the abaxial side, with 3:2 and 1:1 ratios between epicuticular and intracuticular wax layers on each side, respectively. Terpenoids were found mainly in the intracuticular waxes, whereas very-long-chain alkanes and fatty acids accumulated to relatively high concentrations in the epicuticular wax, hence near the true surface of the leaf.