A radioreceptor assay in which iodocyanopindolol is used to determine propranolol and its active metabolites in unextracted serum or plasma.

1986 ◽  
Vol 32 (1) ◽  
pp. 180-183 ◽  
Author(s):  
R P Elkins ◽  
J F Kelly ◽  
B J Rosenberg
Keyword(s):  
Liquid Chromatography ◽  
Beta Blockers ◽  
Isotonic Saline ◽  
Radioreceptor Assay ◽  
Membrane Receptors ◽  
Erythrocyte Membranes ◽  
Clinical Samples ◽  
Active Metabolites ◽  
Adrenergic Antagonist ◽  
Analytical Recovery

Abstract This rapid, sensitive, simple radioreceptor assay (RRA) for l-propranolol and its active metabolites in unextracted samples requires 5 microL of sample, a beta-adrenergic antagonist, 125-l-labeled (-)cyanopindolol (125ICYP), and turkey erythrocyte membrane receptors (Kd = 40 pmol/L). Equal volumes (100 microL) of diluted sample and 125ICYP are incubated with 500 microL of erythrocyte membranes for 30 min. Cold isotonic saline (2.5 mL) is added, and the mixture is centrifuged. The concentration of drug that inhibited receptor binding by 50% (IC50) was l-propranolol, 1.5 micrograms/L; d-propranolol, 243 micrograms/L; and 4-hydroxypropranolol, 8.8 micrograms/L. Analytical recovery of propranolol added to serum was 93 to 120%; results for 138 clinical samples tested by this method and by liquid chromatography correlated well (r = 0.96). Results correlated strongly (r = 0.98) for 23 clinical samples tested by RRA and analyzed for both propranolol and 4-hydroxypropranolol by liquid chromatography. The sensitivity of this RRA was 0.3 micrograms/L, and both intra- and interassay CVs were less than 12%. Modifications of this method could permit testing of other nonselective beta-blockers.

A highly specific radioreceptor assay for the active circulating form of atrial natriuretic factor in human plasma.

1988 ◽  
Vol 34 (11) ◽  
pp. 2275-2279 ◽  
Author(s):  
H Ong ◽  
A De Léan ◽  
C Gagnon
Keyword(s):  
Human Plasma ◽  
Atrial Natriuretic Factor ◽  
Zona Glomerulosa ◽  
Radioreceptor Assay ◽  
Membrane Receptors ◽  
Clinical Samples ◽  
Minimum Detectable Concentration ◽  
Natriuretic Factor ◽  
Detectable Concentration ◽  
Atrial Natriuretic

Abstract This highly sensitive radioreceptor assay (RRA) for the active circulating form of atrial natriuretic factor (ANF), fragment 99-126, in human plasma requires 125I-labeled ANF, bovine zona-glomerulosa membrane receptors, and amiloride HCl. The amiloride elicits an increase in the binding affinity of ANF to its receptors. ANF is extracted from human plasma with "Sep-Pak" cyano cartridges. After a 90-min incubation at 25 degrees C, bound and free fractions are separated by filtration. The ANF concentration that inhibits receptor binding of the radioligand by 50% is 12.4 fmol of unlabeled ANF per tube. The minimum detectable concentration is 0.2 fmol per tube. Using ANF-supplemented plasma samples, there was a good correlation (r = 0.99) between ANF concentrations found and those expected. Only the active circulating form of ANF fully cross-reacts in this assay, which confirms its high selectivity. Results correlated strongly (r = 0.93) for clinical samples tested by RRA and RIA.

A Comprehensive Review on Importance and Quantitation of Atypical Antipsychotic Drugs and their Active Metabolites in Commercial Dosage Forms

2020 ◽  
Vol 16 (8) ◽  
pp. 989-1019
Author(s):  
Habibur Rahman ◽  
S.K. Manirul Haque ◽  
Masoom Raza Siddiqui
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Liquid Chromatography ◽  
Antipsychotic Drugs ◽  
Method Development ◽  
Early Death ◽  
Dosage Forms ◽  
Gas Chromatography Mass Spectrometry ◽  
Active Metabolites ◽  
Chromatography Mass Spectrometry

Background: Schizophrenia is a severe mental illness that affects more than twenty-one million people throughout the world. Schizophrenia also causes early death. Schizophrenia and other related psychotic ailments are controlled by the prescription of antipsychotic drugs, which act by blocking certain chemical receptors in the brain and thus relieves the symptoms of psychotic disorder. These drugs are present in the different dosage forms in the market and provided in a certain amount as per the need of the patients. Objective: Since such medications treat mental disorders, it is very important to have a perfect and accurate dose so that the risk factor is not affected by a higher or lower dose, which is not sufficient for the treatment. For accurate assay of these kinds of drugs, different analytical methods were developed ranging from older spectrophotometric techniques to latest hyphenated methods. Results: The current review highlights the role of different analytical techniques that were employed in the determination and identification of antipsychotic drugs and their metabolites. Techniques such as spectrophotometry, fluorimetry, liquid chromatography, liquid chromatography-mass spectrometry, gas chromatography, and gas chromatography-mass spectrometry employed in the method development of such antipsychotic drugs were reported in the review. Different metabolites, identified using the hyphenated techniques, were also mentioned in the review. The synthesis pathways of few of the metabolites were mentioned. Conclusion: The review summarizes the analyses of different antipsychotic drugs and their metabolites. A brief introduction of illnesses and their symptoms and possible medications were highlighted. Synthesis pathways of the associated metabolites were also mentioned.

scholarly journals Quantification of plasma remdesivir and its metabolite GS-441524 using liquid chromatography coupled to tandem mass spectrometry. Application to a Covid-19 treated patient

2020 ◽  
Vol 58 (9) ◽  
pp. 1461-1468 ◽  
Author(s):  
Jean-Claude Alvarez ◽  
Pierre Moine ◽  
Isabelle Etting ◽  
Djillali Annane ◽  
Islam Amine Larabi
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Half Life ◽  
Limit Of Detection ◽  
Treated Patient ◽  
Internal Standard ◽  
Therapeutic Drug ◽  
Active Metabolites ◽  
Limit Of Quantification ◽  
Positive Mode

AbstractObjectivesA method based on liquid chromatography coupled to triple quadrupole mass spectrometry detection using 50 µL of plasma was developed and fully validated for quantification of remdesivir and its active metabolites GS-441524.MethodsA simple protein precipitation was carried out using 75 µL of methanol containing the internal standard (IS) remdesivir-13C6 and 5 µL ZnSO4 1 M. After separation on Kinetex® 2.6 µm Polar C18 100A LC column (100 × 2.1 mm i.d.), both compounds were detected by a mass spectrometer with electrospray ionization in positive mode. The ion transitions used were m/z 603.3 → m/z 200.0 and m/z 229.0 for remdesivir, m/z 292.2 → m/z 173.1 and m/z 147.1 for GS-441524 and m/z 609.3 → m/z 206.0 for remdesivir-13C6.ResultsCalibration curves were linear in the 1–5000 μg/L range for remdesivir and 5–2500 for GS-441524, with limit of detection set at 0.5 and 2 μg/L and limit of quantification at 1 and 5 μg/L, respectively. Precisions evaluated at 2.5, 400 and 4000 μg/L for remdesivir and 12.5, 125, 2000 μg/L for GS-441524 were lower than 14.7% and accuracy was in the [89.6–110.2%] range. A slight matrix effect was observed, compensated by IS. Higher stability of remdesivir and metabolite was observed on NaF-plasma. After 200 mg IV single administration, remdesivir concentration decrease rapidly with a half-life less than 1 h while GS-441524 appeared rapidly and decreased slowly until H24 with a half-life around 12 h.ConclusionsThis method would be useful for therapeutic drug monitoring of these compounds in Covid-19 pandemic.

scholarly journals Analysis of Active Metabolites of Sophora flavescens for Indoleamine 2,3-dioxygenase and Monoamine Oxidases using Ultra-Performance Liquid Chromatography-Quadrupole time-of-Flight Mass Spectrometry

2018 ◽  
Vol 13 (12) ◽  
pp. 1934578X1801301 ◽  
Author(s):  
Mi Hyeon Park ◽  
Seong Mi Lee ◽  
Sung-Kyun Ko ◽  
Kyeong Yeol Oh ◽  
Jung-Hee Kim ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
High Performance ◽  
Time Of Flight ◽  
Sophora Flavescens ◽  
Active Metabolites ◽  
Ongoing Research ◽  
Monoamine Oxidases ◽  
Indoleamine 2,3 Dioxygenase ◽  
Flight Mass Spectrometry

As part of ongoing research on natural products derived from medicinal plants for enzyme inhibition, known dibenzoyl derivatives (1–3, 11 and 20), pterocarpans (4, 15 and 19), flavanones (5, 7, 10, 12–14, 18, 21–24, 26, 27, 29, 31–33, 35, 36, and 38–46), flavones (6, 16, 28, 30 and 37), isoflavones (8 and 17), furocoumarins (9), and chalcones (25 and 34) have been tentatively identified within fractions of Sophora flavescens roots (SFR) using the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTof-MS) technique. The extract and column fractions inhibited indoleamine 2,3-dioxygenase (IDO) and monoamine oxidases (MAOs) differently depending on the metabolite groups. The majority of rich fractions were shown to have residual activities of 49–59% at 10 μg/mL (IDO) and 11.7–34.9% at 50 μg/mL (MAOs) or below. In the total ion current (TIC) chromatogram, significant markers for the metabolites of the bioactive-guided fractions were identified; pterocarpans (4, 15 and 19), flavanones (5, 10, 12–14, 18, 21–23, 26, 29 31–33, 35, 36, and 38–46), isoflavones (8 and 17), furocoumarins (9), dibenzoyl derivatives (11 and 20), flavones (16, 28, 30 and 37), and chalcones (25 and 34) were evaluated among forty-six analyzed metabolites. Possible bioactive markers could be deduced using a data library and previous references, and information regarding spectroscopic characterization and optimal target metabolites was obtained.

Radioreceptor Assay for Quantifying FK-506 Immunosuppressant in Whole Blood

1992 ◽  
Vol 38 (7) ◽  
pp. 1307-1310 ◽  
Author(s):  
J N Murthy ◽  
Y Chen ◽  
V S Warty ◽  
R Venkataramanan ◽  
J G Donnelly ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Enzyme Immunoassay ◽  
Whole Blood ◽  
Binding Protein ◽  
Radioreceptor Assay ◽  
Fk 506 ◽  
Blood Concentrations ◽  
Chromatographic Columns ◽  
Analytical Recovery

Abstract We describe a quantitative radioreceptor assay (RRA) for quantifying FK-506 in whole blood. FK-506 extracted from whole blood with a cyclohexyl-sorbent column competes with [3H]dihydro-FK-506 for binding to a partially purified preparation of FK-506 binding protein (FK-BP). Free and protein-bound FK-506 are separated on LH 20 Sephadex chromatographic columns. We compared the results of this method with those of an enzyme immunoassay that uses a monoclonal antibody: r = 0.97, Sy/x = 0.039. Between-day precisions (CV) at FK-506 concentrations of 8 and 17 micrograms/L were 9.2% and 8.2%, respectively. Within-run precisions were 5.9%, 8.1%, and 9.4%, respectively, at 4, 8, and 15 micrograms/L. Analytical recovery, evaluated at 5, 10, 15, 20, and 25 micrograms/L for FK-506 added to whole blood, ranged from 98% to 103%. The assay can reliably quantify FK-506 blood concentrations between 1.0 and 25 micrograms/L.

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