The natural origin secondary metabolites have been considered as one of the richest source of new chemical entities with vast array of structural diversity and complexity. The natural compounds have played significant and crucial part in the development of number of therapeutic agents for various diseases especially in the cancer and infectious disease segment. The vast structural and molecular diversity of chemicals present in natural sources inspired medicinal chemist from ages to explore the chemotypes for the innovation and design of new pharmaceuticals and chemical entities. The design of diverse libraries of natural product congeners or derivatives can be achieved using various approaches and strategies to expand the natural product frameworks. Modifying common reactive molecular fragments in natural extracts is an effective strategy for creating pharmacologically active compounds. Various extraction and purification techniques, such as high performance liquid chromatography and supercritical fluid extraction along with membrane-based technologies, are employed to isolate these bioactive compounds.Direct crude extract modification of natural products is an interesting and recent strategy to evolve new chemical entities with diversity in structure and pharmacophore. The reactive chemical moieties present in most of the natural products can be engineered chemically by treating them with particular reagents to yield chemically modified extracts or semi-synthetic molecules constituting distinct libraries with enhanced chemo-diversity and improved pharmacology. This review aims to present latest developments in the synthesis of natural product-inspired medicinal compound libraries via direct chemical modification of crude extracts.
Detecting z-drugs, a sedative-hypnotic medication, is also misused for criminal activities. Therefore, the analysis of urine samples is crucial for clinical and forensic purposes. We conducted a study where we developed, validated, and compared an analytical method for simultaneously detecting z-drugs in urine samples. Our approach uses the QuEChERS method for sample preparation, combined with liquid chromatography (LC) and gas chromatography (GC) coupled with tandem mass spectrometry (MS/MS). We optimized the QuEChERS method to effectively extract z-drugs from urine samples while minimizing matrix effects and achieving high recovery rates. After extraction, we split the samples into two parts for analysis using LC-MS/MS and GC-MS/MS. We validated our methods, and the results showed good linearity over a broad concentration range (1-200 ng/mL) for each z-drug. The limits of detection and quantification were within clinically relevant ranges, ensuring sensitivity for detecting z-drugs in urine samples. We compared the two chromatographic techniques by analyzing a set of urine samples spiked with known concentrations of z-drugs using both LC-MS/MS and GC-MS/MS methods and then applied to the real samples. The results were statistically analyzed to assess any significant differences in accuracy and precision above 95 %, and both methods offered reliable and consistent results with the samples as well. In conclusion, our analytical method coupled with both LC-MS/MS and GC-MS/MS using the QuEChERS approach provides a comprehensive and robust solution for the simultaneous detection of z-drugs in urine samples. The choice between the two chromatographic techniques can be based on the specific z-drugs of interest and the required analytical performance. This method holds promise for applications in clinical toxicology, forensic analysis, and monitoring z-drug usage.
Tramadol (TD) has been prescribed frequently in many countries for more than 40 years, but there is a risk of its misuse and trafficking. As a result, drug analysis has numerous legal and socially relevant implications, making it an essential part of modern analytical chemistry. Thus, the method for the detection of TD and its phase I and phase II metabolites in human urine has been developed and validated using a rapid and efficient approach combining liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization. The sample preparation was best performed using dispersive liquid–liquid microextraction. Analysis was performed using an HyPRITY Cl8 column, and isocratic elution with methanol: water (35:65) with 0.2% formic acid was used. TD and its metabolites were detected at 264.2 (TD/M0) with a base peak at 58.2, 250.3758 (M1), 250.3124 (M2), 236.3976 (M3), 222.5361 (M4), and 236.4475 (M5) m/z peaks. TD showed linearity between 0.1 and 160 ng/mL (R2 = 0.9981). The accuracy ranged from 95.56 to 100.21% for the three concentration levels, while the between- and within-day RSD ranged from 1.58 to 3.92%. The absolute TD recovery was 96.29, 96.91, and 94.31% for the concentrations of 5, 50, and 150 ng/mL, respectively. TD’s phase I metabolites, M1–5 along with nine phase II metabolites, such as sulfo- and glucurono-conjugated metabolites, oxidative TD derivatives, and sulfo-conjugated metabolites were also identified in the urine samples. The pharmacokinetics and metabolism data given provide information for the design of possible future research disorders, evaluating drug mechanism and neurotoxicity and for the effective application screening of TD.
The significance and desire for preliminary testing approaches that are straightforward, quick, selective, affordable, and practical for use in the field are highlighted by the increasing enormous amounts of potentially illegal samples being seized worldwide. The “z-drugs,” which include zolpidem, zopiclone, and eszopiclone, are non-benzodiazepine medications used to treat insomnia. z-drugs are short-term solutions for sleeplessness and anxiety but have a long history of abuse and misuse. The extensive list is primarily utilized for drug-facilitated crimes and drug dependence. The presumptive color spot test for z-drugs, such as zolpidem, zopiclone, and eszopiclone, has been created and validated in this study. In the preliminary identification of zolpidem, zopiclone, and eszopiclone, no color spot test has been documented as per the literature. The color spot test is the most essential and routinely used technique for identifying any unknown sample substance. The color test method was proven to provide high-quality, dependable presumptive test findings and satisfy standards for preliminary screening usage. Validation experiments demonstrate that, at room temperature, the color change is specific to the zolpidem, zopiclone, and eszopiclone classes and unaffected by the common cutting agent’s presence. It was discovered that 5, 10, and 6 ppm were the operational limit of detection of the sample present against the reagents 0.1% diphenyl carbazone, aqueous potassium iodoplatinate, and modified cobalt thiocyanate reagent, respectively. The color test is immediate and validated with other substances of a similar category and 10 ppm was the operational limit of detection.
The utilization and misuse of prescription and controlled medications are expanding globally. However, the kind of substance abused may contrast from one country to another, but few drugs expand their horizons due to misused capabilities, expansion of the darknet, and increase in the Internet Connecting World. One of them is tramadol, a widely misused drug worldwide, which enforcement agencies recently noticed. In treating moderate to severe pain, a racemic combination of tramadol is employed. The non-medical utilization of narcotic drugs, i.e., tramadol, is a quick arising general medical issue prompting expanding calls for planning alterations to existing policies, reconnaissance, research, and wellbeing advancement measures. Tramadol addicts typically have a history of substance usage, and studies show that the number of tramadol abusers is increasing, particularly in some Middle Eastern Nations. This review article finds the trends of analytical methods toward identification in pharmaceutical preparation and toxicological samples such as hair, urine, blood, and saliva. In the last 20 years, various analytical tools such as UV–visible spectroscopy, HPTLC, HPLC, LC–MS, GC, GC–MS, NMR, Fluorescence Spectroscopy, Capillary Electrophoresis, Electrochemical sensors have been used for the identification of drugs in pharmaceutical preparation and toxicological samples. Forensic Scientists can only rely on quick and easy methods to perform. This evaluation aims to give forensic scientists, pharmaceutical companies, and toxicologists the best solution for identifying tramadol acquired in the chemistry and toxicological divisions of various laboratories.
Drug-facilitated sexual assault (DFSA) is a type of sexual savagery against an individual debilitated by a psychealtering substance, such as alcohol or “date rape drugs”. It is estimated that 75% of all acquaintance rapes involve alcohol or drugs. When used with alcohol, drugs can result in a loss of consciousness and a loss of the ability to consent to sexual intercourse. Most DFSA victims are women, and the culprits are men, although men can also be victims. The psychoactive substance most commonly relatedto DFSA is alcohol. However, recreational drug use levels are rising, and drug markets expand, providing faster and cheaper ways to incapacitate a victim. Using drugs for non-consensual sexual activity has led to the introduction of terms such as “date rape drugs” and “drink spiking.”
Nowadays, everyone in their life so stressed that the person is mentally not well. Generally, people do not want to seek out the eternal solution for it. People go for an immediate solution so that they can easily find an answer for his or her illnesses or issue. Mostly, people choose drugs, so instantly can either disregard or can ignore the emotions of oneself during that issue. Drug abuse is not only a crucial public health issue in India but also worldwide. Z-drugs are currently new for the criminals to use for the various criminal acts, which will incorporate child abuse, drug-facilitated sexual assaults (DFSA), and various other crimes. The Z-drugs like zolpidem, zopiclone, and zaleplon hailed because of the innovative hypnotics, an improvement to standard benzodiazepines in the management of a sleeping disorder. Z-drugs have critical mesmerizing impacts by diminishing rest idleness and improving sleep quality; however, the span of sleep might not substantially be expanded. Improper prescribing is another method of controlled drug diversion. This problem differs from doctor shopping and prescription fraud; therein, the latter situations involve abusers attempting to deceive or mislead those medical professionals who are doing their jobs responsibly. Presently, sexual abuse is being worked out in many various ways, and every person in public or offenders knows that if some suspicious item utilized, they can effectively be caught. In this way, sedative-hypnotic currently Z-drugs are accessible and can be utilized for abuse, and nobody will be able to recognize the mans-rea of an individual, whether the person could be a close relative or a stranger. The objective of this work is to meticulously study the Z-drugs and their use and abuse in society. Z-drugs are modern-day replacement of benzodiazepines, which are somewhere being utilized illegally, which could be a considerable concern nationwide.