KEYWORDS: Ions, Signal to noise ratio, Medicine, Interference (communication), Mass spectrometry, Chemical compounds, Latex, Medical toxicology, Reliability, Telecommunications
Methadone is an opioid used in medicine as an analgesic and antidependent maintenance in opioid dependent patients. It is used in the substitution treatment for heroin or other opiates. Methadone belongs to the category of special drugs with a very high potential for dependence and a low lethal dose [1]. Mass spectrometry is an optoelectronic method for determining organic substances by comparing their mass spectrum with mass spectra found in the NIST, Wiley, PMW, and other mass spectrum libraries. In the case of biological products, substances of interest, biotic or xenobiotics may be "hidden" from the noise of the analyzed matrix. A method was developed on a gas chromatograph coupled with a Varian Mass Spectrometer (GC-MS) [2, 3]. The authors presented two methods of increasing sensitivity and signal / noise ratio for the identification of methadone and its metabolites by dissociating ion-specific parent ion for methadone and its metabolites to obtain an MS/MS spectrum.
GHRP-2, also known as Pralmorelin, is a synthetic peptide drug. It acts as ghrelin/growth-hormone secretagogue receptor agonist, being the first drug of this class introduced clinically. It's used, in a single dose formulation, as a diagnostic agent for growth hormone deficiency (GHD). Administration of GHRP-2 increases the plasmatic concentration of growth hormone. It was clinically tested for tratment of GHD and pituitary dwarfism. GHRP-2 has performance enhancing potential and is prohibited for athletes in section S2: Peptide Hormones, Growth Factors, Related Substances, And Mimetics of WADA (World Antidoping Agency) Prohibited List. In this work we developed and validated a screening method for GHRP-2 and it's two metabolites from urine on LC-HRMS (liquid chromatography coupled with high resolution mass spectrometry)(Q Exactive Plus from Thermo Scientific) and LC-MS/MS triple quadrupole (liquid chromatography coupled with mass spectrometry) (ABSciex QTrap 5500). The validation parameters evaluated were limit of detection, matrix effects, identification criteria, specificity, carry-over and extraction recovery. the evaluated parameters are in accordance with WADA technical documents, both methods being applicable for doping control application.
The increase in the number of cases of breast cancer required the development of new pharmaceutical formulas, letrozole being one of the drugs used for this purpose. Treatment with this drug requires detection and monitoring of these substances1. In the doping control of athletes, letrozole is a forbidden substance. Letrozole is included in the Prohibited List of World Anti-Doping Agency (WADA) at the Sections Hormone and Metabolic modulators, Aromatase inhibitors, selective estrogen receptor modulators (SERMs) and other anti-estrogenic substances2,3. For the analysis of these compounds, the technique of choice is the liquid-chromatography tandem mass spectrometry technique (LC-MS/MS). Due to the metabolism of the substance, it is required the analysis of both the compound and the metabolite bis-(4- cyanophenyl)methanol by LC-MS/MS. In the WADA Technical Document TD2018MRPL, the Minimum Required Performance Levels for Detection and Identification of Non-threshold Substances (MRPL) for anti-estrogenic substances is 20 ng/mL2,4. This paper discloses the optimization of the LC-MS/MS detection parameters of letrozol and letrozol metabolite.
Meldonium is an anti-ischemia drug developed in 1970 by Ivars Kalvins at the USSR Latvia Institute of organic synthesis. Meldonium is reportedly capable of providing clinical benefit for those suffering from heart conditions, such as low blood flow to the heart and angina, as well as neurodegenerative disorders and bronchopulmonary diseases. It appears that the medical utility of meldonium derives mostly from its ability to modulate cellular energy metabolism1. This may be due to the drug lowering the consumption of fatty acids, while increasing utilization of carbohydrates for the production of energy. In short, meldonium is advertised as an energy-efficiency catalyst. Since 1 January 2016, it has been on the World Anti-Doping Agency (WADA) list of substances banned from use by athletes. In this work a screening and a confirmation method for Meldonium from urine were developed and validated on LC-MS/MS triple quadrupole (liquid chromatography coupled with mass spectrometry ) (ABSciex QTrap 5500). The validation parameters evaluated were limit of detection, matrix effects, identification criteria, specificity, carry-over and extraction recovery. The evaluated parameters are in accordance with WADA technical documents, both methods being applicable for doping control application.
This article highlights using liquid chromatography and the MRM method [1], the presence of fentanyl and norfentanyl [2] in a biological sample, in this case urine. In the method you can see the presence of each segment in the ion of the substance, obtained by ElectroSpray ionization [1], for which the confirmation is desired. The time of acquisition and the potential collision used to obtain it are specified.
The MRM method is performed with a varying concentration gradient of between 10% and 65% [3] over a 9 minute acquisition time at a constant flow rate of 0.3 ml / minute. The gradient increases from 10% to 40% in the first two minutes, then increases from 40% to 65% over the next 3 minutes. The 65% concentration remains for the next 4 minutes.
Establishing an optoelectronic method for the determination of synthetic cannabinoids and their metabolites is necessary because synthetic cannabinoids are a group of psychoactive compounds designed to mimic the effects of marijuana. These compounds are usually sprayed on natural plants in order to be smoked. Several synthetic cannabinoids can be found on these smoked plants simultaneously. Their effective dose is lower than that of natural marijuana but with high psychoactive potency [1]. Due to their high potential for abuse and availability, these compounds are considered to be narcotic drugs. Thus, there has been an increased demand for the development of sensitive, reliable, robust and sustainable analytical methods for the identification and quantification of these compounds by clinical, forensic and toxicological laboratories [2].
The method presented in the paper will be based on liquid chromatography with a mass spectrometer detector (LCMS/ MS). The paper aims to obtain, using the developed method, the mass spectra of synthetic cannabinoids and their metabolites. The mass spectrum represents the relative abundance of ions resulting from an ionization process of a family of molecules. This is a unique feature for each compound, which allows identification of a substance from a matrix of unknown substances [3].
Our research team is seeking to implement new ways to validate the performance of the biomedical optoelectronic analytical instruments used in Doping Control Laboratory (DCL). The compliance of the instrumental method with international standard of laboratory (ISL) and technical documents (TD) of World Anti-Doping Agency (WADA) is critical in quality assurance, providing precise and accurate results.
The performance level achieved using the innovative method “decision chart” based on “six sigma metric” tool applied to the immunoassay analyses of luteinizing (LH) and chorionic gonadotropin (hCG) hormones, proves the excellent respectively good quality of the testing process, which meet our set goal - performance higher than 4-sigma level.
Using six sigma metric tool, our laboratory was able not only to evaluate performance of our instrumental methods, but also to implement changes to our quality control (QC) charts, to reduce number of internal QCs and calibration expenses as well as reducing troubleshooting.
In order to establish a continuous quality control improvement, verifying the implementation of our quality goals, the quality manager can evaluate analytical performance based on analytical QC data and update the Westgard quality charts.
Tramadol is an opioid drug used to treat moderate to moderate pain, which has two different mechanism of action. The first is due to binding to the opioid receptor, and the second is due to the inhibition of serotonin and norepinephrine reabsorption. Due to its hallucinogenic effects, tramadol is also used as a drug of abuse [1]. It is necessary to identify tramadol and its metabolites in urine specimens either for correct dosing of the tramadol in pain therapy, for monitoring the effectiveness of addiction treatment, or for acute poisoning with this opioid compound [2]. An optoelectronic gas chromatographic method coupled with mass spectrometry is presented to determine tramadol and its metabolites in urine samples [3].
Mass spectrometry is an optoelectronic method of identifying organic substances by comparing their mass spectrum of the analyte with the mass spectra deposited in the mass spectrum libraries of the system. High Pressure Liquid Chromatography (HPLC) coupled with Mass Spectrometry (MS) has as main objective the identification of drugs with a molecular molecule of less than 1500 amu (atomic mass units) [1]. To identify the biological products of antidepressants SSRIs have been deposited in the mass-spectra of the MI library, mass spectra obtained in a HPLC-MS interface with ElectroSpray Interface (ESI) or Atmospheric Pressure Chemical Ionization (APCI). In the paper are presented the mass spectra of selective serotonin reuptake inhibitors (SSRIs): citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, obtained on a HPLC system MS equipped with ESI or APCI.
Platinum is a malleable, ductile metal, silvery white, with atomic number 78 and atomic weight 195.09. We can find it in nature mainly as isotopes: Pt194 (32.9%), Pt195 (33.8%) și Pt196 (25.3%). Of all platinum metals, platinum has the most uses and it’s the most abundant and most easily to be processed.
Its use in auto catalysts results in environmental contamination of crowded cities and high-traffic roads. In medicine, Pt is used as a cytostatic drug. Specific platinum complexes, especially cis-diamminedichloroplatinum (II) (cisplatin), Cis-[oxalate (trans-1-1,2- diaminocyclohexane)] platinum(II) (oxaliplatin) and cis-diammine (1,1- cyclobutanedicarboxylato) platinum(II) (carboplatin), used in therapeutic practice [1,2]. Determination of the Pt concentration in biological samples provides medical personnel with useful information on the efficacy of the cytostatic treatment. An optoelectronic method for determining the concentration of Pt in urine, blood and hair samples collected from patients undergoing cytostatic treatment with platinum-based products is presented. To determine the concentration of Pt in biological products was used: Atomic Absorption Spectrometer model AAS-880, Atomization in the graphite furnace model GT 100, Programable Sample Dispenser PSD - Varian. Platinum concentrations of biological samples collected from platinum, based cytotoxic patients are presented. The presented method can be used to monitor platinumbased chemotherapy with platinum compounds. Graphite Furnace Atomic Absorption Spectroscopy (GF-AAS) method presented is sensitive, reproducible, and relatively easy to apply with an acceptable cost.
KEYWORDS: Contamination, Optoelectronics, Mass spectrometry, Chlorine, Spectroscopy, Ions, Spectrophotometry, Chemical elements, Chemical analysis, Scientific research
A great variety of toxic substances has been and is used for plant protection. If these substances were not used, agricultural production would reduce worldwide by 40%. The most effective but also the most toxic substances used as pesticides are reversible inhibitors of cholinesterase are phosphorus-containing substances, organophosphorus compounds (OPs). Some of the agents have direct cholinergic activity [1]. OPs, mainly used in pest control, as an alternative to hydrocarbons, chlorinated care persist for a long time in the environment. These substances are also very toxic for humans [2].
In order to avoid accidental contamination of the population with xenobiotics pesticides, the European Union issued "Regulation (EU) No 915/2010 on ensuring compliance with maximum permitted levels of pesticide residues in and on foodstuffs of plant and animal origin and assessment of consumer exposure to these residues [3]. The list includes 175 pesticides, of which 36 (20%) are OPs.
Optoelectronics has made an important contribution to understanding the life and the impact of xenobiotics on it. The development of spectrophotometry or spectrometry techniques in the field of UV-VIS-IR and mass spectrometry allowed scientists in the field of bio-science to better understand the mysteries of life or to characterize the impact of some elements or chemicals on it [4].
It’s presented an optoelectronic gas chromatographic method coupled with mass spectrometry is used to determine OPs that may be present in control sample (standard mixture) for food, soil or water.
Papaverine is an opiate alkaloid used in the primary treatment of visceral spasms, cardiac and cerebral vasospasms, and occasionally for the treatment of erectile dysfunction [1]. Although found in opium poppy, papaverine differs both in structure and pharmacological action for opioid analgesics, morphine and related substances [2].
Papaverine is used to treat gastrointestinal tract spasms, bile ducts, ureters as a cerebral and coronary vasodilator, subarachnoid hemorrhage [3] and a coronary artery bypass [4]. Papaverine is used as a smooth muscle relaxant in microsurgery if it is applied directly to blood vessels. In the treatment of erectile dysfunction, a papaverine gel has recently been used [5]. Also, in combination with other drugs, it is commonly used in cryopreservation of blood vessels [6, 7].
Papaverine is a direct relaxing smooth muscle, which is attributed to its ability to inhibit phosphodiesterase. It can be administered for peripheral cerebral and coronary circulation. It can also be used for vascular disorders, for gastrointestinal disorders as an antispasmodic and against cough. However, its use for the latest recommendations should be regarded with caution [8].
For these reasons, the determination of papaverine in urine samples is very important [2]. Identification is preferably by GC-MS or HPLC-MS chromatographic techniques [9].
Polysaccharide-based plasma volume expanders (PVEs) such as hydroxyethyl starch (HES) is on Prohibited List of World Anti-Doping Agency (WADA) because it can prevent dehydration and reduce haematocrit values to mask erythropoietin abuse. The aim of this study is to establish time consuming and reliable methods for doping control screening and confirmation of HES in urine samples. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) with the same column: 5μm Zorbax SB-C18 was used for detection and confirmation without further sample preparation. The method was validated for the parameters: specificity and matrix effect, limit of detection (250μg/mL), identification capability, carryover, robustness. The results of the both method were found to be suitable for the detection and confirmation of hydroxyethylstarch.
Glycerol is the key constituent to triglycerides and is an important compound participating in the lipid metabolism. It is an endogenous compound found in small amounts in human blood and urine. In high doses it can cause migraine, nausea, thirst1. The present degree has purpose the developing and validating a Gas-Chromatography- Tandem Mass Spectrometry (GC-MS) method accurate, rapid and easy to identify and quantify the glycerol analyte in urine samples. The applied analytical technique is based on derivation of the urine sample evaporated with MSTFA/NH4I/ethantiol derivatizing reagent. By this reaction, the hydroxyl functions of glycerol are converted to silyl derivatives, compounds having boiling points lower than the original compounds, this facilitating their GC-MS assay. For estimating the glycerol content, the method are monitored the mass fragments characteristic of the compound of interest – m/z 205, 218 and 293 and an ion corresponding to the deurated analog-m/z 2082.
KEYWORDS: Ions, Mass spectrometry, Chromatography, Optoelectronics, Sodium, Signal to noise ratio, Reliability, Telecommunications, Information technology, Medicine
Drug abuse consists of the use by a subject without a medical recommendation, in quantities or with nonrecommended methods. Substance abuse also refers to their use in order to increase intellectual or physical performance, against the rules established by society. Substance abuse involves the chronic use of non-medical chemicals for hedonistic or entheogenic purposes [1]. Drugs such as alcohol, antidepressants, amphetamine, barbiturates, benzodiazepines, cannabinoids, glue, cocaine, hallucinogens, metacular, narcotics, opiates, sedatives, stimulants and some organic solvents can be named [2]. Substance abuse can cause criminal or antisocial behavior, may generate long-term changes in personality [3].
Cocaine has major toxic effects on the body. Treatment of cocaine poisoning is complex. The main sales are those that can lead to patient death. For the proper treatment of any inoculation, it is necessary to identify the xenobiotic that generated it. The presence of metabolites, in the case of cocaine - ethylbenzoylcogene (EBE), provides information on the time of administration of the xenobiotic.
Gas chromatography or liquid chromatography coupled with mass spectrometry is an optoelectronic method that can identify the presence of cocaine and / or EBE from biological samples. In order to increase the sensitivity of the method, a special mass metrology technique - MS/MS can be used [4, 5].
Platinum (Pt) is a malleable, ductile, silver-white metal with atomic number 78 and an atomic weight of 195.09. Platinum is found in nature in metallic state, alloyed with small amounts of iron, copper, other platinum metals, and sometimes with little gold. This ore appears as granules or nuggets, weighing from a few milligrams to a few pounds, scattered in a silicate (olivine and piroxene). Urine samples (10 ml spot), were collected from patients admitted to the Clinical Toxicology Section. Expert literature recommends the determination of platinum in the normal population of the area as the amount of platinum present in the environment differs. For determination of platinum in biological products an installation consisting of Atomic Absorption Spectrometer Model AAS-880, Atomizing in graphite furnace model GT 100, Autosampler model PSD - Varian. Graphite Furnace Atomic Absorption Spectroscopy (GF-AAS) optoelectronic method presented is a fast, reproducible, with a very good sensitivity for monitoring population or staff exposed to platinum and its compounds.
Cobalt is a chemical element with symbol Co and atomic number 27 and atomic weight 58.93. 59 Co is the only stable cobalt isotope and the only isotope to exist naturally on Earth. Cobalt is the active center of coenzymes called cobalamin or cyanocobalamin the most common example of which is vitamin B12. Vitamin B12 deficiency can potentially cause severe and irreversible damage, especially to the brain and nervous system in the form of fatigue, depression and poor memory or even mania and psychosis. In order to study the degree of deficiency of the population with Co or the correctness of treatment with vitamin B12, a modern optoelectronic method for the determination of metals and metalloids from biological samples has been developed, Graphite Furnace – Atomic Absorption Spectrometer (GF– AAS) method is recommended. The technique is based on the fact that free atoms will absorb light at wavelengths characteristic of the element of interest. Free atoms of the chemical element can be produced from samples by the application of high temperatures. The system GF-AAS Varian used as biological samples, blood or urine that followed the digest of the organic matrix. For the investigations was used a high – performance GF-AAS with D2 – background correction system and a transversely heated graphite atomizer. As result of the use of the method are presented the concentration of Co in the blood or urine of a group of patient in Bucharest. The method is sensitive, reproducible relatively easy to apply, with a moderately costs.
Antidepressants were found in 1950. In the 1990s there was a new generation of antidepressants. They act on the level of certain neurotransmitters extrasinpatic by its growth. After their mode of action antidepressants may be: SSRIs (Selective Serotonin Reuptake Inhibitors); (Serotonin-Norepinephrine Reuptake Inhibitors); SARIs (Serotonin Antagonist Reuptake Inhibitors); NRIs (Norepinephrine Reuptake Inhibitors); NDRIs (Norepinephrine-Dopamine Reuptake Inhibitors) NDRAs (Norepinephrine-Dopamine Releasing Agents); TCAs (Tricyclic Antidepressants); TeCAs (Tetracyclic Antidepressants); MAOIs (Monoamine Oxidase Inhibitors); agonist receptor 5-HT1A (5- hydroxytryptamine); antagonist receptor 5-HT2; SSREs (Selective Serotonin Reuptake Enhancers) and Sigma agonist receptor.
To determine the presence of antidepressants in biological products, it has been used a system HPLC-MS (High Performance Liquid Chromatography – Mass Spectrometry) Varian 12001. The system is equipped with APCI (Atmospheric Pressure Chemical Ionization) or ESI (ElectroSpray Ionization) interface. To find antidepressants in unknown samples is necessary to recognize them after mass spectrum. Because the mass spectrum it is dependent on obtaining private parameters work of HPLC-MS system, and control interfaces, the mass spectra library was filled with the mass spectra of all approved antidepressants in Romania. The paper shows the mass spectra obtained in the HPLCMS system.
Of all platinum metals, platinum has the most uses and it’s the most abundant and most easily to be processed. Its use in auto catalysts results in environmental contamination of crowded cities and high-traffic roads. In medicine, Pt is used as a cytostatic drug. In order to study the degree of contamination of the population with Pt or the correctness of treatment with Pt, it has been developed a method for its determination from urine or blood samples with a system Graphite Furnance - Atomic Absorption Spectrometer, (GF-AAS) Varian. There are presented the methods of sampling processing for blood or urine that followed the digest of the organic matrix. In the determination of the operating parameters for the system GF-AAS, was aimed the reducing of the nonanatomic absorbance by optimizing the drying temperatures, the calcination and atomization temperatures and the removal of the nonanatomic absorbance with D2 lamp. As a result of the use of the method are presented the concentrations of Pt in the blood or urine of a group of patients in Bucharest, a city with heavy traffic of vehicles. GF-AAS method presented is sensitive, reproducible, and relatively easy to apply with an acceptable cost. With this method, the concentration of Pt can be determined from blood and urine, both in order to establish the degree of contamination with Pt and for monitoring cancer therapy with platinum compounds.
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