Drugs In Biological Samples Research Articles

Quantitative Analysis of Drugs in a Mimetic Tissue Model Using Nano-DESI on a Triple Quadrupole Mass Spectrometer.

Mass spectrometry is a powerful analytical technique used at every stage of the pharmaceutical research process. A specialized branch of this method, mass spectrometry imaging (MSI), has emerged as an important tool for determining the spatial distribution of drugs in biological samples. Despite the importance of MSI, its quantitative capabilities are still limited due to the complexity of biological samples and the lack of separation prior to analysis. This makes the simultaneous quantification and visualization of analytes challenging. Several techniques have been developed to address this challenge and enable quantitative MSI. One such approach is the mimetic tissue model, which involves the incorporation of an analyte of interest into tissue homogenates at several concentrations. A calibration curve that accounts for signal suppression by the complex biological matrix is then created by measuring the signal of the analyte in the series of tissue homogenates. Herein, we use the mimetic tissue model on a triple quadrupole mass spectrometer (QqQ) in multiple reaction monitoring mode to demonstrate the quantitative abilities of nanospray desorption electrospray ionization (nano-DESI) and compare these results with those obtained using atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI). For the tested compounds, our findings indicate that nano-DESI achieves lower standard deviations than AP-MALDI, resulting in superior limits of detection for the studied analytes. Additionally, we discuss the limitations of the mimetic tissue model in the quantification of certain analytes and the challenges involved with the implementation of the model.

Enantioselective Separation and Pharmacokinetics of a Chiral 1,4-Dihydropyrimidine Derivative in Rats: A Combined Chromatography and Docking Approach.

Chirality in 1,4-Dihydropyrimidines influences their pharmacological properties and synthetic strategies. Enantiomers of chiral drugs often exhibit different pharmacokinetic profiles. Therefore, separating and studying individual enantiomers is crucial to optimize drug efficacy and safety. Enantiomeric separation of ±4-(4-chlorophenyl)-6-methyl-2-oxo-N-(O-toyl)-1,2,3,4-tetrahydropyrimidine-5-carboxamide (DP-1), which is a 1,4-Dihydropyrimidine derivative is achieved on CHIRALCEL® OD-H column (particle size: 5 μm, inner diameter: 4.6 mm, length:150 mm), following by investigating the kinetic properties of (R) and (S) enantiomers. The separation was achieved with a mobile phase composed of 70% (v/v) isopropyl alcohol and 30% (v/v) n-hexane. For the bioanalytical study, acetonitrile was used to precipitate the rat plasma samples and validated the method according to USFDA guidelines. The validated bioanalytical method was then successfully applied to determine the pharmacokinetic parameters of the drug in biological samples. Molecular modeling techniques, specifically docking simulations, were employed to predict the elution order of DP-1 enantiomers. The docking results revealed moderate binding interactions between the enantiomers and the chiral stationary phase (CSP), which aligns with the theoretical expectation that stronger interactions lead to longer retention times on the column.

High-performance liquid chromatography coupled to Orbitrap mass spectrometry for screening of common new psychoactive substances and other drugs in biological samples.

The complexity of the drug market and the constant updating of drugs have been challenging issues for drug regulatory authorities. With the emergence of new psychoactive substances (NPS) and the nonmedical use of prescription drugs, forensic and toxicology laboratories have had to adopt new drug screening methods and advanced instrumentation. Using high-performance liquid chromatography coupled with Orbitrap mass spectrometry, we developed a screening method for common NPS and other drugs. Two milliliters of mixed solvent of n-hexane and ethyl acetate (1:1, v:v) were added to 500 μL of blood or urine sample for liquid-liquid extraction, and methanol extraction was used for hair samples. The developed method was applied to 3897 samples (including 332 blood samples, 885 urine samples, and 2680 hair samples) taken from drug addicts in a province of China during 2019-2021. For urine and blood samples, the limits of detection (LODs) ranged from 1.68 pg/mL to 10.7 ng/mL. For hair samples, the LODs ranged from 3.30 × 10-5 to 4.21 × 10-3 ng/mg. The matrix effects of urine, blood, and hair samples were in the range of 47.6%-121%, 39.8%-139%, and 6.35%-118%, respectively. And the intra-day precision was 3.5%-6.0% and the inter-day precision was 4.18%-9.90%. Analysis of the actual samples showed an overall positive detection rate of 58.9%, with 5.32% of the samples indicating the use of multiple drugs.

Measurement of isoniazid in tuberculosis patients using finger sweat with creatinine normalisation: A controlled administration study

BackgroundInsufficient exposure and poor compliance with anti-tuberculosis (TB) medications are risk factors for treatment failure and the development of drug resistance. Measurement of drugs in biological samples, such as blood and saliva, can be used to assess adherence and make dose adjustments by therapeutic drug monitoring (TDM). Finger sweat testing is a convenient and non-invasive method to monitor patients. ObjectivesTo assess the feasibility of finger sweat testing for medication adherence and as a semi-quantitative tool for TDM analysis. MethodsTen patients provided finger sweat, blood and saliva samples following a controlled dose of isoniazid. Samples were analysed by liquid chromatography-mass spectrometry. ResultsIsoniazid can be detected in finger sweat 1–6 h following administration at typically prescribed dosages. The normalisation of isoniazid to creatinine increases the correlation between finger sweat and serum isoniazid concentration and provides a means to account for inconsistent sample volumes. ConclusionWe describe the time-course measurement of isoniazid (or drug-to-creatinine ratio) in finger sweat compared to the pharmacokinetic profile in blood for the first time. This technique, adaptable for other drugs, could reduce the burden on clinics and improve patient experience.

A Thiophene Functionalized Hf(IV)-Organic Framework for the Detection of Anti-Neoplastic Drug Flutamide and Biomolecule Hemin and Catalysis of Friedel-Crafts Alkylation.

Development, rapid detection and quantification of anticancer drugs in biological samples are crucial for effective drug monitoring. The present work describes the design of a Hf(IV)-based metal-organic framework (MOF) (1) by the reaction between Hf(IV) ion and 2-(thiophene-2-carboxamido)terephthalic acid linker with the surface area of 571 m2 g-1. Desolvated MOF (1') displayed highly discriminative fluorescence sensing properties for the antineoplastic drug flutamide and biomolecule hemin in an aqueous medium in the presence of co-existing biomolecules and ions. The MOF's response time for sensing flutamide and hemin was less than 5 s with low detection limits of 1.5 and 0.08 nM, respectively. Additionally, 1' also demonstrated recyclability up to five cycles and maintained its sensing ability across different pH media, various water samples, and biological fluids. Experimental and theoretical analyses suggested photoinduced electron transfer and inner-filter effect in the presence of flutamide and Förster resonance energy transfer in the presence of hemin are most likely reasons behind the fluorescence quenching of MOF. Furthermore, the MOF demonstrated catalytic activity in Friedel-Crafts alkylation reactions, providing a 96 % yield with slight decay in its activity over four uses. The enhanced activity of 1' compared to Hf-BDC and Hf-BDC-NH2 (BDC: 1,4-benzenedicarboxylic acid) is due to the functionalized thiophene moieties through hydrogen bond donating sites, confirmed by a series of control experiments.

Ultrasonically Assembled 0-D Zirconium Oxide on TiO2 Nanorod for a Sensitive Determination of Antibiotic Drug in Biological Samples

Biological, food, and water samples were used to determine the amount of Furazolidone (FUZ) in a variety of applications, including health and nutrition, diagnosis/treatment, pharmacological research, and food/drug quality monitoring. Using hydrothermal and ultrasonication strategies, new type of TiO2 (1D) and ZrO2 (0D) (TiO2/ZrO2) nanocomposites were prepared for FUZ determination. Then the prepared nanocomposite was characterization under X-ray diffraction, field emission scanning electron microscopy, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, ultra violet visible spectroscopy, and the electrochemical property of the material was characterized by electrochemical impedance spectroscopy and cyclic voltammetry (CV). In addition, detection of FUZ was analyzed by electroanalytical studies such as CV and differential pulse voltammetry (DPV). This proposed TiO2/ZrO2/GCE sensor exhibits excellent electrochemical characteristics, including excellent linearity (0.01–537.22 μM), nanomolar detection limit (19 nM), and encouraging sensitivity (0.35 μA μM−1cm−2) and it shows greater selectivity, repeatability, and longer storage stability. Along with concerned realizability, the primed sensor was analyzed over biological samples that reveal good recovery in real samples.

Electrochemical DNA-nano biosensor for the detection of Goserelin as anticancer drug using modified pencil graphite electrode.

Goserelin is an effective anticancer drug, but naturally causes several side effects. Hence the determination of this drug in biological samples, plays a key role in evaluating its effects and side effects. The current studies have concentrated on monitoring Goserelin using an easy and quick DNA biosensor for the first time. In this study, copper(II) oxide nanoparticles were created upon the surface of multiwalled carbon nanotubes (CuO/MWCNTs) as a conducting mediator. The modified pencil graphite electrode (ds-DNA/PA/CuO/MWCNTs/PGE) has been modified with the help of polyaniline (PA), ds-DNA, and CuO/MWCNTs nanocomposite. Additionally, the issue with the bio-electroanalytical guanine oxidation signal in relation to ds-DNA at the surface of PA/CuO/MWCNTs/PGE has been examined to determination Goserelin for the first time. It also, established a strong conductive condition to determination Goserelin in nanomolar concentration. Thus, Goserelin's determining, however, has a 0.21 nM detection limit and a 1.0 nM-110.0 µM linear dynamic range according to differential pulse voltammograms (DPV) of ds-DNA/PA/CuO/MWCNTs/PGE. Furthermore, the molecular docking investigation highlighted that Goserelin is able to bind ds-DNA preferentially and supported the findings of the experiments. The determining of Goserelin in real samples has been effectively accomplished in the last phase using ds-DNA/PA/CuO/MWCNTs/PGE.

Challenges and future trends of forensic toxicology to keep a cut above the rest.

Forensic toxicology faces several challenges in research and daily practice, including new drugs and futuristic technologies requiring innovative testing methods and continuous education and training of professionals. One of the most pressing issues in recent years is the emergence of novel psychoactive substances, often created by modifying the chemical structure of existing drugs to produce compounds with similar effects that are not yet regulated and lack standardized references. To overcome this challenge, forensic toxicologists have employed a range of analytical methods, including qualitative and quantitative analysis using highly sensitive technologies such as liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS), which are the most reliable and accurate methods for detecting drugs in biological samples. Liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS) is becoming the gold standard for detecting controlled substances, their derivatives and metabolites. Despite advancements in testing methods, challenges persist in forensic toxicology. As such, the field must invest in research and development to improve testing methods, utilize cutting-edge technologies, increase funding for training programs, and promote multidisciplinary interactions.

How new nanotechnologies are changing the opioid analysis scenery? A comparison with classical analytical methods.

Opioids such as heroin, fentanyl, raw opium, and morphine have become a serious threat to the world population in the recent past, due to their increasing use and abuse. The detection of these drugs in biological samples is usually carried out by spectroscopic and/or chromatographic techniques, but the need for quick, sensitive, selective, and low-cost new analytical tools has pushed the development of new methods based on selective nanosensors, able to meet these requirements. Modern sensors, which utilize "next-generation" technologies like nanotechnology, have revolutionized drug detection methods, due to easiness of use, their low cost, and their high sensitivity and reliability, allowing the detection of opioids at trace levels in raw, pharmaceutical, and biological samples (e.g. blood, urine, saliva, and other biological fluids). The peculiar characteristics of these sensors not only have allowed on-site analyses (in the field, at the crime scene, etc.) but also they are nowadays replacing the gold standard analytical methods in the laboratory, even if a proper method validation is still required. This paper reviews advances in the field of nanotechnology and nanosensors for the detection of commonly abused opioids both prescribed (i.e. codeine and morphine) and illegal narcotics (i.e. heroin and fentanyl analogues).

Photosubstitution and photoreduction of a diazido platinum(IV) anticancer complex.

The hyphenation of HPLC with its high separation ability and ICP-MS with its excellent sensitivity, allows the analysis of Pt drugs in biological samples at the low nanomolar concentration levels. On the other hand, LC-MS provides molecular structural confirmation for each species. Using a combination of these methods, we have investigated the speciation of the photoactive anticancer complex diazido Pt(IV) complex trans, trans, trans-[Pt(N3)2(OH)2(py)2] (FM-190) in aqueous solution and biofluids at single-digit nanomolar concentrations before and after irradiation. FM-190 displays high stability in human blood plasma in the dark at 37 °C. Interestingly, the polyhydroxido species [{PtIV(py)2(OH)4} + Na]+ and [{PtIV(py)2(N3)(OH)3} + Na]+ resulting from the replacement of azido ligands, as determined by LC-MS, were the major products after photoirradiation of FM-190 with blue light (463 nm). This finding suggests that such photosubstituted Pt(IV) tri- and tetra-hydroxido species could play important roles in the biological activity of this anticancer complex. Density Functional Theory (DFT) and Time-Dependent DFT (TDDFT) calculations show that these Pt(IV) species arising from FM-190 in aqueous media can be formed directly from a singlet excited state. The results highlight how speciation analysis (metallomics) can shed light on photoactivation pathways for FM-190 and formation of potential excited-state pharmacophores. The ability to detect and identify photoproducts at physiologically-relevant concentrations in cells and tissues will be important for preclinical development studies of this class of photoactivatable platinum drugs.

Molecularly imprinted solid-phase extraction combined with non-ionic hydrophobic deep eutectic solvents dispersed liquid-liquid microextraction for efficient enrichment and determination of the estrogens in serum samples

Hormonal drugs in biological samples are usually in low concentration and highly intrusive. It is of great significance to enhance the sensitivity and specificity of the detection process of hormone drugs in biological samples by utilizing appropriate sample pretreatment methods for the detection of hormone drugs. In this study, a sample pretreatment method was developed to effectively enrich estrogens in serum samples by combining molecularly imprinted solid-phase extraction, which has high specificity, and non-ionic hydrophobic deep eutectic solvent-dispersive liquid-liquid microextraction, which has a high enrichment ability. The theoretical basis for the effective enrichment of estrogens by non-ionic hydrophobic deep eutectic solvent was also computed by simulation. The results showed that the combination of molecularly imprinted solid-phase extraction and deep eutectic solvent-dispersive liquid-liquid microextraction could improve the sensitivity of HPLC by 33∼125 folds, and at the same time effectively reduce the interference. In addition, the non-ionic hydrophobic deep eutectic solvent has a relatively low solvation energy for estrogen and possesses a surface charge similar to that of estrogen, and thus can effectively enrich estrogen. The study provides ideas and methods for the extraction and determination of low-concentration drugs in biological samples and also provides a theoretical basis for the application of non-ionic hydrophobic deep eutectic solvent extraction.

Standardization of the analytical procedure based on deep eutectic solvent for the extraction and measurement of tricyclic antidepressants drugs in post-mortem blood samples

Measuring drugs in post-mortem blood samples is one of the most important challenges in forensic medicine. The development of sensitive analytical techniques for the measurement of drugs in biological samples is of great use in forensic medicine. In this research an easy, safe and environmental friendly vortex-assisted liquid phase microextraction (VA−LPME) based on deep eutectic solvent (DES) followed by high performance liquid chromatography−ultraviolet detector (HPLC−UV) was developed for the extraction, preconcentration and analysis of tricyclic antidepressants drugs (TCAs) in post-mortem blood samples. DES synthesized from thymol as hydrogen bond acceptor (HBA) and ethylene glycol (EG) as hydrogen bond donor (HBD) with a molar ratio of 2:1 was used as an extractant. After adding DES to the sample solution, the resulting mixture was vortexed in order to increase the contact surface and increase the extraction efficiency. Next, phase separation was done using centrifugation. Some effective parameters on the extraction were studied and optimized. Under the optimum conditions, intra- and inter-day %RSDs of the method based on 7 replicate measurements of 100 μg L–1 of TCAs in blood samples were in the range of 2.4–5.1 and 3.7–6.8 %, respectively. The analytical performance of the method showed linearity over the concentration of 3–500 μg L−1 with the detection limits ranging from 1.0–2.0 μg L−1. The trueness of the method was confirmed by spiking different concentrations of TCAs in real blood samples and obtaining relative recoveries in the range of 91.2–108 %.

Development and Validation of LC-MS/MS Method for Determination of Cytisine in Human Serum and Saliva.

Cytisine (CYT) is a quinolizidine alkaloid used for nicotine addiction treatment. Recent clinical trial data regarding cytisine confirm its high effectiveness and safety as a smoking cessation treatment. CYT's popularity is growing due to its increased availability and licensing in more countries worldwide. This increased use by smokers has also resulted in an urgent need for continued drug research, including developing appropriate analytical methods for analyzing the drug in biological samples. In this study, a simple, fast, and reliable method combining hydrophilic interaction liquid chromatography and electrospray ionization quadrupole time of flight mass spectrometry (HILIC/ESI-QTOF-MS) for the determination of CYT in human serum and saliva was developed and validated. This was undertaken after the previous pre-treatment of the sample using solid-phase extraction (SPE). A hydrophilic interaction liquid chromatography (HILIC) column with a silica stationary phase was used for chromatographic analysis. In a linear gradient, the mobile phase consisted of acetonitrile (ACN) and formate buffer at pH 4.0. The proposed method was fully validated and demonstrated its sensitivity, selectivity, precision, and accuracy. The method was successfully applied to determine CYT in serum and, for the first time, in saliva. The findings indicate that saliva could be a promising non-invasive alternative to measure the free concentration of CYT.

Quantification of sedative-hypnotics in human urine and plasma via polystyrene-based solid phase extraction-LC-MS/MS analysis

Owing to the adverse effects of the overuse of common sedative-hypnotics on human health, the development of an efficient analytical method for the detection of drugs in clinical emergencies and forensic science is significant. Although conventional analytical methods, such as immunoassay, liquid chromatography (LC), gas chromatography, and mass spectrometry (MS) are reliable, they exhibit drawbacks such low-throughput screening and high costs. Thus, in this study, we developed a novel high-throughput method consisting of a polystyrene-based solid phase extraction (SPE) and an LC with tandem MS analysis for the detection of drugs in biological samples and investigated its precision and reliability via the detection of twelve sedative-hypnotics in human urine and plasma samples. Good linear relationship (r ≥ 0.99) were achieved within the concentration range of 0.1–20 ng/mL for the 12 analytes in urine samples. Whereas, in the plasma samples, the correlation coefficient was greater than 0.99 in the concentration range 1–100 ng/mL for lorazepam and clonazepam and in the range 0.5–100 ng/mL for the remaining analytes. The intra- and inter-day precision, autosampler and freeze–thaw stabilities, and lower limit of quantitation (LLOQ) for all twelve analytes in the urine and plasma samples were favorable. Furthermore, sedative-hypnotics were detected in clinical samples obtained from the Hebei General Hospital using this method. These results indicated that the analytical method proposed in this study can be effectively applied in toxicology screening and drug abuse monitoring.The method developed in this study could be applied in clinical and forensic toxicology laboratories for sedative-hypnotic drug screening, providing support for drug abuse monitoring and clinical diagnosis.

Fluorescence “light-up” sensor based on ligand/SiO2@NH2@cyanuric chloride nanoparticle interactions in alliance with salt dehydration for berberine detection

Berberine (BBR) is an important anti-inflammatory drug for the treatment of intestinal diseases. The quantification of BBR is required in clinical medicine because long-term or excessive intake can lead to drug resistance and adverse effects. In this study, SiO2@NH2@cyanuric chloride (CNCl) nanoparticles (NPs) were successfully prepared by covalently incorporating CNCl onto the surface of SiO2 NPs. Furthermore, a novel fluorescence “light-up” sensor for assaying BBR was established based on the interaction between BBR and SiO2@NH2@CNCl NPs. Although BBR was non-emissive in aqueous media, its fluorescence was considerably augmented because of the interaction with the as-prepared SiO2@NH2@CNCl NPs, and the enhancement factor was approximately three times larger than that of pure SiO2 NPs. Compared with SiO2 NPs, SiO2@NH2@CNCl NPs can interact with BBR through electrostatic interactions and π-π stacking. These interactions restricted the intramolecular motion and charge transfer of BBR, resulting in fluorescence enhancement. The sensor was sensitive, with a linear response over a concentration range of 25–2500 nM (R2 = 0.9905) and a detection limit (3σ/k) of 4.7 nM, and it had good selectivity for BBR in the presence of bovine serum albumin, amino acids, and metal ions. When the sensor was applied to real serum samples, rapid extraction and salt dehydration occurred to improve the efficiency of pretreatment, and satisfactory standard recovery rates (95%–96%) were achieved even when only small amounts of acetonitrile was used for protein precipitation. This strategy could serve as a reference for other studies requiring the analysis of drugs in biological samples.

An "ON-OFF" fluorescent sensor based on a novel zinc-based flower-like structured metal-organic framework for sequential detection of deferasirox and tigecycline

Deferasirox (DEF) is essential for patients with thalassemia requiring long-term transfusion therapy. Tigecycline (TIGE) is a first-line drug for the clinical treatment of complex, severe bacterial infections. The two drugs can be coordinated to treat Pseudomonas aeruginosa infections. Easy and efficient techniques for monitoring these two drugs in biological samples are few. Metal–organic framework (Zn-MOF) prepared from zinc nitrate hexahydrate and dithioglycolic acid has a flower structure. Interestingly, Zn-MOF can cause DEF to aggregate on it and induce DEF luminescence. The principle may be that Zn-MOF limits the vibration and rotation of DEF to avoid its nonradiative jump, which triggers aggregation-induced emission (AIE) and exhibits intense fluorescence. Further investigation revealed that TIGE could decompose Zn-MOF, thus alleviating the inhibitory effect of Zn-MOF on DEF and reducing the fluorescence intensity of DEF@Zn-MOF. A DEF/TIGE detection biosensor was created based on the fluorescence "turn-on" effect of Zn-MOF on DEF and the fluorescence "turn-off" effect of TIGE on DEF@Zn-MOF. The proposed technique was subsequently used to identify DEF/TIGE levels in pharmaceuticals and human plasma. The mean values for the percentage of the labeled amount of DEF/TIGE in DEF dispersible tablets/TIGE injection were 104.5 and 104.9%, respectively. The detection limits for the fluorescence detection of DEF and TIGE were 3.6 and 1.2 nM, respectively. This fluorescence assay is the first application of MOF to the simultaneous detection of DEF and TIGE and has the advantages of rapid sensitivity and high selectivity, providing a new strategy for drug detection.

LC-MS/MS-MS3 for the Determination and Quantification of Δ9-Tetrahydrocannabinol and Metabolites in Blood Samples.

Due to the high prevalence of cannabinoids in forensic toxicology analysis, it is crucial to have an efficient method that allows the use of a small sample amount and that requires a minimal sample preparation, for the determination and quantification of low concentrations. A simple, highly selective and high throughput liquid chromatography tandem mass spectrometry methodology (LC-MS/MS-MS3) was developed for the determination and quantification of ∆9-tetrahydrocannabinol (THC), 11-hydroxy-∆9- tetrahydrocannabinol (THC-OH) and 11-nor-9-carboxy-∆9-tetrahydrocannabinol (THC-COOH), in blood samples. Chromatographic analysis of THC, THC-OH, and THC-COOH and their deuterated internal standards was preceded by protein precipitation (PPT) of 0.1 mL of blood samples with acetonitrile. Chromatographic separation was achieved by use of an Acquity UPLC® HHS T3 (100 mm x 2.1mm i.d., 1.8 μm) reversed-phase column, using a gradient elution of 2 mM aqueous ammonium formate, 0.1% formic acid, and methanol at a flow rate of 0.4 mL/min, with a run time of 10 minutes. For the MS/MS-MS3 analysis, a SCIEX QTRAP® 6500+ triple quadrupole linear ion trap mass spectrometer was used via electrospray ionization (ESI), operated in multiple reaction monitoring (MRM) and linear ion trap mode (MS3). The method was validated in accordance with internationally accepted criteria and guidelines, and proved to be selective and linear between 0.5-100 ng/mL (r2>0.995). The lower limits of quantification (LLOQ) corresponded to the lowest concentrations used for the calibration curves. The coefficients of variation obtained for accuracy and precision were <15%. The mean recoveries were between 88.0-117.2%, for the studied concentration levels (1 ng/mL, 5 ng/mL and 50 ng/mL). No significant interfering compounds, matrix effects or carryover were observed. The validated method provides a sensitive, efficient and robust procedure for the quantification of cannabinoids in blood, using LC-MS/MS-MS3 and a sample volume of 0.1 mL. This work is also a proof of concept for using LC-MS3 technique to determine drugs in biological samples.

Fabrication of impedimetric sensor based on metallic nanoparticle for the determination of mesna anticancer drug

Electrochemical impedance spectroscopy (EIS) is a highly effective technique for studying the surface of electrodes in great detail. EIS-based electrochemical sensors have been widely reported, which measure the charge transfer resistance (Rct) of redox probes on electrode surfaces to monitor the binding of target molecules. One of the protective drugs against hemorrhagic cystitis caused by oxazaphosphorine chemotherapy drugs such as ifosfamide, cyclophosphamide and trophosphamide is Mesna (sodium salt of 2-mercaptoethanesulfonate). The increase in the use of Mesna due to the high consumption of anti-cancer drugs, the determination of this drug in biological samples is of particular importance. So far, no electrochemical method has been reported to measure Mesna. In this research, a novel impedimetric sensor based on a glassy carbon electrode (GCE) modified with oxidized multiwalled carbon nanotubes (MWCNTs)/gold nanoparticle (AuNPs) (denoted as Au NPs/MWCNTs/GCE) for impedimetric determination of Mesna anticancer drug was developed. The modified electrode materials were characterized by field emission scanning electron microscopy (FESEM), energy dispersive X-ray (EDX), and EIS. The electrochemical behavior of Mesna at the surface of Au NPs/MWCNTs/GCE was studied by an impedimetric method. The detection mechanism of Mesna using the proposed impedimetric sensor relied on the increase in the Rct value of [Fe (CN)6]3−/4− as an electrochemical probe in the presence of Mesna compared to the absence of Mesna as the analyte. Under the optimum condition, which covered two linear dynamic ranges from 0.06 nmol L−1 to 1.0 nmol L−1 and 1.0 nmol L−1 to 130.0 µmol L−1, respectively. The detection limit was 0.02 nmol L−1. Finally, the performance of the proposed sensor was investigated for Mesna electrochemical detection in biological samples.

Development of electrospun nanofibers based on Poly (vinyl alcohol) for thin film solid-phase microextraction of antidepressant drugs in biological samples

Today, antidepressants are widely used and it is important to determine their trace amounts due to harmful consequences. Here, a new nano sorbent was reported for the simultaneous extraction and determination of three types of antidepressant drugs (Clomipramine (CLO), Clozapine (CLZ), and Trimipramine (TRP) by the thin-film solid-phase micro-extraction (TFME-μSPE) method followed by the Gas Chromatography-flame ionization detector (GC-FID) analysis. So, the compound poly (vinyl alcohol) (PVA)/citric acid(CA)/β-cyclodextrin/Bi2S3@g-C3N4 nano sorbent was constructed by electrospinning technique. Then, nano sorbent was studied to optimize the many parameters impacting the extraction performance. Electrospun nanofiber has a large surface area, high porosity, and homogeneous morphology with a uniform bead-free structure. In optimal conditions, the limits of detection and quantification were calculated to be 0.15–0.03 ng mL−1 and 0.5–0.1 ng mL−1, respectively. The dynamic linear range (DLR) was in the range of 0.1 to 1000 ng mL−1 for CLO and CLZ, and 0.5 to 1000 ng mL−1 for TRP with correlation coefficients (R2) of 0.999. The relative standard deviations (RSDs) were achieved in the range of 4.9–6.8% (intra-day, n = 4) and 5.4–7.9% (inter-day, n = 3) in the period of 3 days. Finally, the capability of the method was evaluated to simultaneously measure trace amounts of antidepressants aqueous sample with desirable extraction efficiency (78 to 95%).

Ultrasensitive and rapid detection of methamphetamine in forensic biological fluids using fluorescent apta-nanobiosensors based on CdTe quantum dots

Rapid and sensitive detection of illegal and addictive drugs in biological samples is essential in various organizations such as forensic medicine, diagnostic clinics, and anti-narcotics headquarters. Methamphetamine (MA) is the second most addictive psychoactive substance, which poses a major threat to global health. This study aimed to propose a novel apta-nano biosensor for ultrasensitive and fast detection of MA in biological fluids. The water-soluble apta-nano biosensor was prepared with the ligand-exchange method using the replacement of thioglycolic acid (TGA) molecules at the surface of QDs with thiolated MA aptamer. The fluorescence intensity of QDs was increased after modification with aptamer and then decreased by the addition of the target molecule (MA) due to the formation of the aptamer-MA complex. The apta-nano biosensor was used as an ultrasensitive and selective fluorescent sensor for the determination of MA with a linear range of 1.34 ± 0.25 × 10−10–1.24 ± 0.07 × 10−7 mol/L, and the detection limit 40.34 ± 1.05 × 10−12 mol/L. The fabricated apta-nano biosensor can be successfully applied for the determination of MA in forensic biological fluids (blood plasma and urine) with satisfactory analytical results. Also, obtained results were evaluated with liquid chromatography-tandem mass spectrometry (LC-MS-MS).