This is advantageous to offer stringent specificity to the NE-tagged proteins, which are readily to be detected, quantitated, and purified.
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Aciclovir may be quantitated in plasma or serum to monitor for drug accumulation in patients with renal dysfunction or to confirm a diagnosis of poisoning in acute overdose victims.
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Salicylate, the major metabolite of methyl salicylate, may be quantitated in blood, plasma or serum to confirm a diagnosis of poisoning in hospitalized patients or to assist in an autopsy.
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Shotgun lipidomics was developed by Richard W. Gross and Xianlin Han, by employing ESI intrasource separation techniques. Individual molecular species of most major and many minor lipid classes can be fingerprinted and quantitated directly from biological lipid extracts without the need for chromatographic purification.
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Atomoxetine may be quantitated in plasma, serum or whole blood in order to distinguish extensive versus poor metabolizers in those receiving the drug therapeutically, to confirm the diagnosis in potential poisoning victims or to assist in the forensic investigation in a case of fatal overdosage.
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Acetylfentanyl may be quantitated in blood, plasma or urine by liquid chromatography-mass spectrometry to confirm a diagnosis of poisoning in hospitalized patients or to provide evidence in a medicolegal death investigation. Postmortem peripheral blood acetylfentanyl concentrations have been in a range of 89–945 μg/L in victims of acute overdosage.
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Swelling could be restored by therapeutics that repair the CFTR protein (CFTR modulators), indicating that individual responses to CFTR modulating therapy could be quantitated in a preclinical laboratory setting. Schwank et al. also demonstrated that the intestinal cystic fibrosis organoid phenotype could be repaired by CRISPR-Cas9 gene editing in 2013. Follow-up studies by Dekkers et al.
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In addition, the microglia also undergo rapid proliferation in order to increase their numbers. From a strictly morphological perspective, the variation in microglial form along the continuum is associated with changing morphological complexity and can be quantitated using the methods of fractal analysis, which have proven sensitive to even subtle, visually undetectable changes associated with different morphologies in different pathological states.
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Potassium is now quantified by ionization techniques, but at one time it was quantitated by gravimetric analysis. Reagents used to precipitate potassium salts include sodium tetraphenylborate, hexachloroplatinic acid, and sodium cobaltinitrite into respectively potassium tetraphenylborate, potassium hexachloroplatinate, and potassium cobaltinitrite. The reaction with sodium cobaltinitrite is illustrative: : 3K+ \+ Na3[Co(NO2)6] → K3[Co(NO2)6] + 3Na+ The potassium cobaltinitrite is obtained as a yellow solid.
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Desoxypipradrol may be quantitated in blood, plasma or urine by liquid chromatography-mass spectrometry to confirm a diagnosis of poisoning in hospitalized patients or to provide evidence in a medicolegal death investigation. Blood or plasma desoxypipradrol concentrations are expected to be in a range of 10–50 μg/L in persons using the drug recreationally, >100 μg/L in intoxicated patients and >600 μg/L in victims of acute overdosage.
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Briefly, instead of labelling antibodies (or other biological probes) with fluorochromes, each antibody is labelled with a distinct combinations of lanthanides. When the sample of interest is analysed by ICP-MS in a specialised flow cytometer, each antibody can be identified and quantitated by virtue of a distinct ICP "footprint". In theory, hundreds of different biological probes can thus be analysed in an individual cell, at a rate of ca. 1,000 cells per second.
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DOC may be quantitated in blood, plasma or urine by gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry to confirm a diagnosis of poisoning in hospitalized patients or to provide evidence in a medicolegal death investigation. Blood or plasma DOC concentrations are expected to be in a range of 1–10 μg/L in persons using the drug recreationally, >20 μg/L in intoxicated patients and >100 μg/L in victims of acute overdosage.
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Strychnine is easily quantitated in body fluids and tissues using instrumental methods in order to confirm a diagnosis of poisoning in hospitalized victims or to assist in the forensic investigation of a case of fatal overdosage. The concentrations in blood or urine of those with symptoms are often in the 1–30 mg/L range.R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1448-1450.
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The mathematics is performed by software provided with the instrument. Alternatively, Kd can be calculated from a gel mobility shift assay in which the same purified protein is incubated with serial dilutions of gel-purified, 32P-end-labelled target oligonucleotide. The incubation reactions are then resolved, over a short period, on a polyacrylamide gel and quantitated using a commercially available imager and software. Kd is calculated via Scatchard analysis using the binding isotherm equation; θb = [peptide]/([peptide] + Kd).
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The antigen diffuses radially into the medium, forming a circle of precipitin that marks the boundary between the antibody and the antigen. The diameter of the circle increases with time as the antigen diffuses into the medium, reacts with the antibody, and forms insoluble precipitin complexes.(1) (2) . The antigen is quantitated by measuring the diameter of the precipitin circle and comparing it with the diameters of precipitin circles formed by known quantities or concentrations of the antigen. .
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AAPS J. 16, 11–14 (2014). Hence and due to their complexity and specific composition mix, such colloidal iron carbohydrate drugs cannot be fully identified, characterized, quantitated and/or described by physiochemical means to define their pharmaceutical properties. Therefore, contradictory to the generic paradigm pathway, relying on a full pharmaceutical identity and sameness in vitro evaluation exercise, they need additional (biological, in vivo) evaluation with a reference product to assess comparability e.g. in tissue targeting in the body.
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Conditions which cause increased rouleaux formation include infections, inflammatory and connective tissue disorders, and cancers (most common in multiple myeloma). It also occurs in diabetes mellitus and is one of the causative factors for microvascular occlusion in diabetic retinopathy. Erythrocyte sedimentation rate closely reflects the extent of aggregation, therefore can be used as a measure of aggregation. Erythrocyte aggregation can also be quantitated by monitoring optical properties of blood during the time course of aggregation process.
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Buprenorphine and norbuprenorphine may be quantitated in blood or urine to monitor use or abuse, confirm a diagnosis of poisoning, or assist in a medicolegal investigation. There is a significant overlap of drug concentrations in body fluids within the possible spectrum of physiological reactions ranging from asymptomatic to comatose. Therefore, it is critical to have knowledge of both the route of administration of the drug and the level of tolerance to opioids of the individual when results are interpreted.
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In addition to arterial blood gas, an anion gap can also differentiate between possible causes. The Henderson-Hasselbalch equation is useful for calculating blood pH, because blood is a buffer solution. In the clinical setting, this equation is usually used to calculate HCO3 from measurements of pH and PaCO2 in arterial blood gases. The amount of metabolic acid accumulating can also be quantitated by using buffer base deviation, a derivative estimate of the metabolic as opposed to the respiratory component.
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Zolpidem may be quantitated in blood or plasma to confirm a diagnosis of poisoning in people who are hospitalized, to provide evidence in an impaired driving arrest, or to assist in a medicolegal death investigation. Blood or plasma zolpidem concentrations are usually in a range of 30–300μg/l in persons receiving the drug therapeutically, 100–700μg/l in those arrested for impaired driving, and 1000–7000μg/l in victims of acute overdosage. Analytical techniques, in general, involve gas or liquid chromatography.
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DEET may be quantitated in blood, plasma or urine by gas or liquid chromatography-mass spectrometry to confirm a diagnosis of poisoning in hospitalized patients or to provide evidence in a medicolegal death investigation. Blood or plasma DEET concentrations are expected to be in a range of 0.3–3.0 mg/L during the first 8 hours after dermal application in persons using the chemical appropriately, >6 mg/L in intoxicated patients and >100 mg/L in victims of acute intentional oral overdose.
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Lorazepam may be quantitated in blood or plasma to confirm poisoning in hospitalized people, provide evidence of an impaired driving arrest or to assist in a medicolegal death investigation. Blood or plasma concentrations are usually in a range of 10–300 μg/l in persons either receiving the drug therapeutically or in those arrested for impaired driving. Approximately 300–1000 μg/l is found in people after acute overdosage. Lorazepam may not be detected by commonly used urine drug screenings for benzodiazepines.
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Codeine and its major metabolites may be quantitated in blood, plasma or urine to monitor therapy, confirm a diagnosis of poisoning or assist in a medico-legal death investigation. Drug abuse screening programs generally test urine, hair, sweat or saliva. Many commercial opiate screening tests directed at morphine cross-react appreciably with codeine and its metabolites, but chromatographic techniques can easily distinguish codeine from other opiates and opioids. It is important to note that codeine usage results in significant amounts of morphine as an excretion product.
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In order to make conclusions about relative intensity a great deal of knowledge and care is required. A common way to get more quantitative information out of a mass spectrum is to create a standard curve to compare the sample to. This requires knowing what is to be quantitated ahead of time, having a standard available and designing the experiment specifically for this purpose. A more advanced variation on this is the use of an internal standard which behaves very similarly to the analyte.
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Carbon monoxide may be quantitated in blood using spectrophotometric methods or chromatographic techniques in order to confirm a diagnosis of poisoning in a person or to assist in the forensic investigation of a case of fatal exposure. A CO-oximeter can be used to determine carboxyhemoglobin levels. Pulse CO-oximeters estimate carboxyhemoglobin with a non-invasive finger clip similar to a pulse oximeter. These devices function by passing various wavelengths of light through the fingertip and measuring the light absorption of the different types of hemoglobin in the capillaries.
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Nuclear DNA evidence can be recovered from blood, semen, saliva, epithelial cells and hair (if the root is still intact). Furthermore, Mitochondrial DNA can be recovered from the shaft of hair, bone and the roots of teeth. For most forensic DNA samples, STR analysis of autosomal short tandem repeats is performed in an attempt to individualize the sample to one person with a high degree of statistical confidence. TaqMan ProbesSTR electropherogram of a three-person mixture Laboratory analysis of DNA evidence involves the sample DNA being extracted, quantitated, amplified, and visualized.
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Since the tags are isobaric and have identical chemical properties, the isotopic variants of the tags appear as a single composite peak at the same m/z value in an MS1 scan with identical liquid chromatography (LC) retention times. During a liquid chromatography-mass spectrometry (LC-MS) analysis, the fragmented peptides produce sequence- specific product ions. These product ions are used to determine the peptide sequence and the reporter tags whose abundances reflect the relative ratio of the peptide in the samples that were combined. The use of MS/MS is required to detect the tags, therefore, unlabeled peptides are not quantitated.
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Presence of amatoxins in mushroom samples may be detected by the Meixner test (also known as the Wieland test). The amatoxins may be quantitated in plasma or urine using chromatographic techniques to confirm a diagnosis of poisoning in hospitalized patients and in postmortem tissues to aid in a medicolegal investigation of a suspected fatal overdosage. In 2020, a monoclonal antibody-based lateral flow immunoassay has been developed that can quickly and selectively detect amatoxins. This test sensitively detects alpha- amanitin and gamma-amanitin (clearly detects 10 ng/mL), and exhibits slightly less detection for beta-amanitin (0.5% cross-reactivity; 2000 ng/mL).
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Mephedrone may be quantitated in blood, plasma or urine by gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry to confirm a diagnosis of poisoning in hospitalised patients or to provide evidence in a medicolegal death investigation. Blood or plasma mephedrone concentrations are expected to be in a range of 50–100 μg/l in persons using the drug recreationally, >100 μg/l in intoxicated patients and >500 μg/l in victims of acute overdosage.L.J. Marinetti and H.M. Antonides. Analysis of synthetic cathinones commonly found in bath salts in human performance and postmortem toxicology: method development, drug distribution and interpretation of results.
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Diamorphine is produced from acetylation of morphine derived from natural opium sources, generally using acetic anhydride. The major metabolites of diamorphine, 6-MAM, morphine, morphine-3-glucuronide, and morphine-6-glucuronide, may be quantitated in blood, plasma or urine to monitor for abuse, confirm a diagnosis of poisoning, or assist in a medicolegal death investigation. Most commercial opiate screening tests cross-react appreciably with these metabolites, as well as with other biotransformation products likely to be present following usage of street-grade diamorphine such as 6-acetylcholine and codeine. However, chromatographic techniques can easily distinguish and measure each of these substances.
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GHB may be quantitated in blood or plasma to confirm a diagnosis of poisoning in hospitalized patients, to provide evidence in an impaired driving, or to assist in a medicolegal death investigation. Blood or plasma GHB concentrations are usually in a range of 50–250 mg/L in persons receiving the drug therapeutically (during general anesthesia), 30–100 mg/L in those arrested for impaired driving, 50–500 mg/L in acutely intoxicated patients and 100–1000 mg/L in victims of fatal overdosage. Urine is often the preferred specimen for routine drug abuse monitoring purposes. Both γ-butyrolactone (GBL) and 1,4-butanediol are converted to GHB in the body.
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Ketamine may be quantitated in blood or plasma to confirm a diagnosis of poisoning in hospitalized patients, provide evidence in an impaired driving arrest or to assist in a medicolegal death investigation. Blood or plasma ketamine concentrations are usually in a range of 0.5–5.0 mg/L in persons receiving the drug therapeutically (during general anesthesia), 1–2 mg/L in those arrested for impaired driving and 3–20 mg/L in victims of acute fatal overdosage. Urine is often the preferred specimen for routine drug use monitoring purposes. The presence of norketamine, a pharmacologically-active metabolite, is useful for confirmation of ketamine ingestion.
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Fluoxetine and norfluoxetine may be quantitated in blood, plasma or serum to monitor therapy, confirm a diagnosis of poisoning in hospitalized person or assist in a medicolegal death investigation. Blood or plasma fluoxetine concentrations are usually in a range of 50–500 μg/L in persons taking the drug for its antidepressant effects, 900–3000 μg/L in survivors of acute overdosage and 1000–7000 μg/L in victims of fatal overdosage. Norfluoxetine concentrations are approximately equal to those of the parent drug during chronic therapy, but may be substantially less following acute overdosage, since it requires at least 1–2 weeks for the metabolite to achieve equilibrium.
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MDMA and MDA may be quantitated in blood, plasma or urine to monitor for use, confirm a diagnosis of poisoning or assist in the forensic investigation of a traffic or other criminal violation or a sudden death. Some drug abuse screening programs rely on hair, saliva, or sweat as specimens. Most commercial amphetamine immunoassay screening tests cross-react significantly with MDMA or its major metabolites, but chromatographic techniques can easily distinguish and separately measure each of these substances. The concentrations of MDA in the blood or urine of a person who has taken only MDMA are, in general, less than 10% those of the parent drug.
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There is some penetration of the blood–brain barrier with brain concentrations reaching 5.3% of those in the blood (measured one hour after a single 2000 mg intravenous dose). Clearance rates range from 9 to 95 ml/min and steady-state concentrations when 800 mg is given twice daily range from 60 μM to 530 μM. The highest brain concentrations of oxiracetam are found in the septum pellucidum, followed by the hippocampus, the cerebral cortex and with the lowest concentrations in the striatum after a 200 mg/kg oral dose given to rats. Oxiracetam may be quantitated in plasma, serum or urine by liquid chromatography with one of several different detection techniques.
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Isobaric mass tags (tandem mass tags) are tags that have identical mass and chemical properties that allow heavy and light isotopologues to co-elute together. All mass tags consist of a mass reporter that has a unique number of 13C substitutions, a mass normalizer that has a unique mass that balances the mass of the tag to make all the tags equal in mass and a reactive moiety that crosslinks to the peptides. These tags are designed to cleave at a specific linker region upon high-energy CID, yielding different-sized tags that are then quantitated by LC-MS/MS. Protein or peptide samples prepared from cells, tissues or biological fluids are labeled in parallel with the isobaric mass tags and combined for analysis.
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To confirm a diagnosis of botulinum toxin poisoning, therapeutically or to provide evidence in death investigations, botulinum toxin may be quantitated by immunoassay of human biological fluids; serum levels of 12–24 mouse LD50 units per milliliter have been detected in poisoned patients. Japanese doomsday cult Aum Shinrikyo produced botulinum toxin and spread it as an aerosol in downtown Tokyo during the 1990s, but the attacks caused no fatalities. During the early 1980s, German and French newspapers reported that the police had raided a Baader-Meinhof gang safe house in Paris and had found a makeshift laboratory that contained flasks full of Clostridium botulinum, which makes botulinum toxin. Their reports were later found to be incorrect; no such lab was ever found.
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IGFBP-3 was first isolated, characterized, and quantitated in human plasma, in 1986. It has well-documented functions in the circulation, in the extracellular environment, and inside cells. It is the main IGF transport protein in the bloodstream, where it carries the growth factors predominantly in stable complexes that contain the binding protein, either IGF-1 or IGF-2, and a third protein called the acid-labile subunit or ALS. For IGFs to reach the tissues from the bloodstream, the circulating complexes are believed to partly dissociate, possibly enhanced by limited proteolysis of IGFBP-3. The IGF-1/IGFBP-3 ratio has sometimes been used as an index of IGF bioavailability in the human circulation, but this ignores IGF-1 binding to other IGFBPs (so the ratio is affected by the concentrations of all six IGFBPs), and the fact that IGF-2, which is three times more abundant than IGF-1 in the bloodstream of adults, occupies the majority of binding sites on circulating IGFBP-3.
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