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1.
Molecules ; 28(18)2023 Sep 08.
Article in English | MEDLINE | ID: mdl-37764300

ABSTRACT

Olaparib (OLA) is a PARP inhibitor drug which has been recently approved by the Food and Drug Administration (FDA) for the treatment of ovarian and breast cancer. A convenient analytical tool for the quantitation of OLA in its dosage form and plasma samples was urgently needed. This study describes, for the first time, the development of two different label-free and sensitive fluorescence-based platforms for the pharmaceutical and bioanalysis of OLA. These platforms were microwell-assisted with a fluorescence microplate reader (MW-FLR) and high-performance liquid chromatography with fluorescence detection (HPLC-FD). Both MW-FLR and HPLC-FD employed the native fluorescence of OLA as an analytical signal. The MW-FLR involved measuring the fluorescence signals in 96-well white-opaque plates. The HPLC-FD involved chromatographic separation of OLA and duvelisib (DUV), as an internal standard on a Nucleosil-CN HPLC column (250 mm length × 4.6 mm i.d., 5 µm particle diameter) with a mobile phase composed of acetonitrile: water (25:75, v/v) pumped at a flow rate of 1.7 mL/min. Elution of OLA and DUV was detected using a fluorescence detector. The optimal conditions of both MW-FLR and HPLC-FD were established, and they were validated according to the guidelines of the International Council for Harmonization for the validation of analytical procedures. The linear ranges of MW-FLR and HPLC-FD were 25-1000 and 5-200 ng/mL, respectively, with limits of detection of 15 and 1.7 ng/mL, respectively. The accuracy and precision of both platforms were confirmed as the recovery values were ≥98.2% and the relative standard deviations (RSD) were ≤2.89%. Both methodologies were satisfactorily applied to the quantitation of OLA in its commercial dosage form (Lynparza® tablets) and plasma samples with high accuracy and precision. The greenness of both MW-FLR and HPLC-FD was assessed using two different multiple parameter-based metric tools, and the results proved their greenness and adherence to the requirements of green analytical approaches. Both platforms have simple procedures and acceptable levels of analytical throughput. In conclusion, the proposed MW-FLR and HPLC-FD are valuable tools for routine use in quality control and clinical laboratories for the quantitation of OLA for the purposes of pharmaceutical quality control, pharmacokinetic studies, and bioequivalence testing.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/drug therapy , Chromatography, High Pressure Liquid/methods , Phthalazines , Tablets/chemistry
2.
J Mol Struct ; 1263: 133104, 2022 Sep 05.
Article in English | MEDLINE | ID: mdl-35465174

ABSTRACT

Remdesivir (REM) is an adenosine triphosphate analog antiviral drug that has received authorization from European Commission and approval from the U.S. Food and Drug Administration for treatment of coronavirus disease 2019 (Covid-19). This study, describes, for the first time, the synthesis of a novel charge transfer complex (CTC) between REM, as electron donor, with chloranilic acid (CLA), as π electron acceptor. The CTC was characterized using different spectroscopic and thermogravimetric techniques. UV-visible spectroscopy ascertained the formation of the CTC in methanol via formation of a new broad absorption band with maximum absorption peak (λmax) at 530 nm. The molar absorptivity (ε) of the complex was 3.33 × 103 L mol-1 cm-1 and its band gap energy was 1.91 eV. The stoichiometric ratio of REM:CLA was found to be 1:1. The association constant of the complex was 1.11 × 109 L mol-1, and its standard free energy was 5.16 × 104 J mole-1. Computational calculation for atomic charges of energy minimized REM was conducted, the site of interaction on REM molecule was assigned and the mechanism of the reaction was postulated. The solid-state CTC was further characterized by FT-IR and 1H NMR spectroscopic techniques. Both FT-IR and 1H NMR confirmed the formation of the CTC and its structure. The reaction was adopted as a basis for developing a novel 96-microwell spectrophotometric method (MW-SPA) for REM. The assay limits of detection and quantitation were 3.57 and 10.83 µg/well, respectively. The assay was validated, and all validation parameters were acceptable. The assay was implemented successfully with great precision and accuracy to the determination of REM in its bulk form and pharmaceutical formulation (injection). This assay is simple, economic, and more importantly, has high throughput property. Therefore, the assay can be valuable for routine in quality control laboratories for analysis of REM's bulk form and pharmaceutical injection.

3.
Article in English | MEDLINE | ID: mdl-35396012

ABSTRACT

Vinpocetine (VIN) is a herbal supplement extracted from the periwinkle plant. It is a multi-action agent, which is used to treat various neurological disorders such as Alzheimer's and Parkinson's disease. Vinpocetine has also anti-inflammatory, analgesic, antioxidant property and treats various thinking and memory problems. Currently, vinpocetine is also available in the market as a dietary supplement to enhance cognition and memory. This profile explains the physicochemical properties, methods of preparation, content of related impurities and different spectroscopical behavior of vinpocetine. It also discusses the reported methods of analysis of the drug, which include Compendial Methods, Electrochemical Methods, Spectrophotometric Methods and Chromatographic Methods of analysis. Furthermore, this profile explains the stability of the drug subjected to stress conditions of acid, alkaline and photolytic degradation. In addition, the clinical applications of the drug, its uses, side effects, dosing information, pharmacokinetics and mechanism of action are also discussed.


Subject(s)
Vinca Alkaloids , Antioxidants , Dietary Supplements , Humans , Memory Disorders/drug therapy , Vinca Alkaloids/analysis , Vinca Alkaloids/pharmacology , Vinca Alkaloids/therapeutic use
4.
Spectrochim Acta A Mol Biomol Spectrosc ; 264: 120287, 2022 Jan 05.
Article in English | MEDLINE | ID: mdl-34455386

ABSTRACT

Duvelisib (DUV) is a is a small-molecule with inhibitory action for phosphoinositide 3-kinase (PI3K). It has been recently approved for the effective treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Novel charge transfer complex (CTC) between DUV, as electron donor, with chloranilic acid (CLA), as π electron acceptor has been synthesized and characterized using different spectroscopic and thermogravimetric techniques. UV-visible spectroscopy ascertained the formation of the CTC in different solvents of varying polarity indexes and dielectric constants via formation of new broad absorption band with maximum absorption peak (λmax) in the range of 488-532 nm. The molar absorptivity of the CTC was dependent on the polarity index and dielectric constant of the solvent; the correlation coefficients were 0.9955 and 0.9749, respectively. The stoichiometric ratio of DUV:CLA was 1:1. Electronic spectral analysis was conducted for characterization of the complex in terms of its electronic constants. Computational calculation for atomic charges of energy minimized DUV was conducted and the site of interaction on DUV molecule was assigned. The solid-state CTC of DUV:CLA (1:1) was synthesized, and its structure was characterized by UV-visible, mass, FT-IR, and 1H NMR spectroscopic techniques. Both FT-IR and 1H NMR confirmed that both CT and hydrogen bonding contributed to the molecular composition of the complex. The reaction was adopted as a basis for developing a novel 96-microwell spectrophotometric assay (MW-SPA) for DUV. The assay limits of detection and quantitation were 0.57 and 1.72 µg/well, respectively. The assay was validated and all validation parameters were acceptable. The method was implemented successfully with great precision and accuracy to the analysis of the DUV in its bulk and capsules.


Subject(s)
Hydrogen , Phosphatidylinositol 3-Kinases , Benzoquinones , Isoquinolines , Purines , Spectroscopy, Fourier Transform Infrared
5.
Drug Des Devel Ther ; 15: 2667-2677, 2021.
Article in English | MEDLINE | ID: mdl-34188446

ABSTRACT

BACKGROUND: Duvelisib (DUV) is a new oral phosphoinositide-3-kinase (PI3K)-δ and PI3K-γ inhibitor. It has been recently granted an accelerated approval for treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). It is also effective in therapy of T-cell lymphoma, solid tumors, and non-Hodgkin's lymphoma. In literature, there is no method valid for quantitation of DUV in human plasma for its therapeutic monitoring and pharmacokinetic studies. PURPOSE: The purpose of this study is the establishment of a highly sensitive HPLC method with fluorescence detection for quantitation of DUV in plasma for its therapeutic monitoring and pharmacokinetic studies of DUV. METHODS: The resolution of DUV and the internal standard (IS) olaparib (OLA) was achieved on Nucleosil CN column, with a mobile phase composed of acetonitrile:water (25:75, v/v) at a flow rate of 1.7 mL min-1. The fluorescence of both DUV and OLA was detected at 410 nm after excitation at 280 nm. The method was validated according to the guidelines of bioanalytical method validation. RESULTS: The method was linear in the range of 5-100 ng mL-1, and its limit of detection (LOD) and limit of quantitation (LOQ) were 2.12 ng mL-1 and 7 ng mL-1, respectively. The precisions of the method were ≤ 8.26%, and its accuracies were ≥ 95.32%. All the other validation parameters were satisfactory. The proposed method was successfully employed to the investigation of the pharmacokinetic profile of DUV in rats following a 25 mg/kg single dose of oral administration. CONCLUSION: The method is characterized with high sensitivity, accuracy, simple sample pretreatment, rapidity, eco-friendly as it consumes low volumes of organic solvent in the mobile phase and has high analysis throughput as its run time was short (~ 10 min).


Subject(s)
Chromatography, High Pressure Liquid/methods , Isoquinolines/pharmacokinetics , Phosphoinositide-3 Kinase Inhibitors/pharmacokinetics , Purines/pharmacokinetics , Animals , Drug Monitoring/methods , Humans , Isoquinolines/analysis , Male , Phosphoinositide-3 Kinase Inhibitors/analysis , Purines/analysis , Rats , Rats, Wistar , Reproducibility of Results , Spectrometry, Fluorescence
6.
Pharmaceuticals (Basel) ; 14(5)2021 Apr 26.
Article in English | MEDLINE | ID: mdl-33926020

ABSTRACT

In the current study, the effect of poloxamer 188 on the complexation efficiency and dissolution of arbidol hydrochloride (ADL), a broad-spectrum antiviral agent, with ß-cyclodextrin (ß-CD) was investigated. Phase solubility studies confirmed a stoichiometry of a 1:1 ratio for both ADL:ß-CD and ADL/ß-CD with a 1% poloxamer 188 system with an AL type of phase solubility curve. The stability constants (K1:1) calculated from the AL type diagram were 550 M-1 and 2134 M-1 for AD:ß-CD and ADL/ß-CD with 1% poloxamer 188, respectively. The binary ADL/ß-CD and ternary ADL/ß-CD with 1% poloxamer 188 complexes were prepared by kneading and a solvent evaporation method and were characterized by aqueous solubility, FTIR, PXRD, DSC and SEM in vitro studies. The solubility (13.1 fold) and release of ADL were markedly improved in kneaded ternary ADL/ß-CD with 1% poloxamer 188 (KDB). The binding affinity of ADL and ß-CD was confirmed by 1H NMR and 2D ROSEY studies. The ternary complex (KDB) was further subjected for in vivo pharmacokinetic studies in rats and a significant improvement in the bioavailability (2.17 fold) was observed in comparison with pure ADL. Therefore, it can be concluded that the solubilization and bioavailability of ADL can be remarkably increased by ADL/ß-CD complexation in the presence of a third component, poloxamer 188.

7.
J Pharm Biomed Anal ; 198: 114023, 2021 May 10.
Article in English | MEDLINE | ID: mdl-33744464

ABSTRACT

Rivaroxaban, indicated for the treatment of atrial fibrillation, deep vein thrombosis, pulmonary embolism, and coronary or peripheral artery disease, is one of the most frequently used direct oral anticoagulants. Therapeutic drug monitoring [TDM] is essential to minimize bleeding and thrombosis during personalized rivaroxaban treatment. An efficient and reliable analytical technique is required to quatify the rivaroxaban during its therapeutic indication. Dried blood spots (DBSs) sampling is a convenient bioanalytical method with minimal invasive blood drawing, long-term stability, and low shipment and storage costs. Therfore, DBS sampling technique is growing rapidly for TDM of drugs in medical care. This study developed an ultra high performance liquid chromatography-tandem mass spectrometry method of quantitating rivaroxaban in DBSs samples using the isotopic labeled analog (rivaroxaban-d4) as an internal standard (IS). Rivaroxaban and IS were separated on an Acquity HILIC column and eluted with a mobile-phase composition of acetonitrile and 20 mM ammonium acetate in the ratio of 95:5 at a flow rate of 0.3 mL/min. The precursor-to-product ion transitions of 436.03 ˃ 144.9 for rivaroxaban and 440.04 ˃ 144.9 for IS were used to quantify in multiple reaction monitoring mode. The method was accurate and precise in the 2.06-1000 ng/mL calibration range without hematocrit and blood spot volume effects. Rivaroxaban was stable in DBSs samples under different anticipated storage and temperature conditions. We observed good correlation between the plasma concentration and the DBSs concentration, indicating that the proposed DBSs method is suitable for monitoring the rivaroxaban concentration using a simple and convenient sample collection procedure.


Subject(s)
Rivaroxaban , Tandem Mass Spectrometry , Chromatography, High Pressure Liquid , Dried Blood Spot Testing , Drug Monitoring , Reproducibility of Results
8.
Drug Des Devel Ther ; 15: 1167-1180, 2021.
Article in English | MEDLINE | ID: mdl-33737805

ABSTRACT

BACKGROUND: Linifanib (LFB) is a multi-targeted receptor tyrosine kinase inhibitor used in the treatment of hepatocellular carcinoma and other types of cancer. The charge-transfer (CT) interaction of LFB is important in studying its receptor binding mechanisms and useful in the development of a reliable CT-based spectrophotometric assay for LFB in its pharmaceutical formulation to assure its therapeutic benefits. PURPOSE: The aim of this study was to investigate the CT reaction of LFB with 2,3-dichloro-3,5-dicyano-1,4-benzoquinone (DDQ) and its application in the development of a novel 96-microwell spectrophotometric assay for LFB. METHODS: The reaction was investigated, its conditions were optimized, the physicochemical and constants of the CT complex and stoichiometric ratio of the complex were determined. The solid-state LFB-DDQ complex was synthesized and its structure was analyzed by UV-visible, FT-IR, and 1H-NMR spectroscopic techniques, and also by the computational molecular modeling. The reaction was employed in the development of a novel 96-microwell spectrophotometric assay for LFB. RESULTS: The reaction resulted in the formation of a red-colored product, and the spectrophotometric investigations confirmed that the reaction had a CT nature. The molar absorptivity of the complex was linearly correlated with the dielectric constant and polarity index of the solvent; the correlation coefficients were 0.9526 and 0.9459, respectively. The stoichiometric ratio of LFB:DDQ was 1:2. The spectroscopic and computational data confirmed the sites of interaction on the LFB molecule, and accordingly, the reaction mechanism was postulated. The reaction was utilized in the development of the first 96-microwell spectrophotometric assay for LFB. The assay limits of detection and quantitation were 1.31 and 3.96 µg/well, respectively. The assay was successfully applied to the analysis of LFB in its bulk and tablets with high accuracy and precision. CONCLUSION: The assay is simple, rapid, accurate, eco-friendly as it consumes low volumes of organic solvent, and has high analysis throughput.


Subject(s)
Indazoles/chemistry , Phenylurea Compounds/chemistry , Models, Molecular , Molecular Structure , Proton Magnetic Resonance Spectroscopy , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared
9.
Spectrochim Acta A Mol Biomol Spectrosc ; 252: 119482, 2021 May 05.
Article in English | MEDLINE | ID: mdl-33571740

ABSTRACT

The tyrosine kinase inhibitors (TKIs) are chemotherapeutic drugs used for targeted therapy of various types of cancer. In literature, there is no existing universal chromogenic reagent used for development of spectrophotometric assay for all TKIs regardless the diversity of their chemical structures. This work discusses, for the first time, the experimental and computational evaluation of chloranilic acid (CLA) as a universal chromogenic reagent for developing a novel 96-microwell spectrophotometric assay (MW-SPA) for TKIs. The reaction of CLA with seven TKIs was examined in different organic solvents of various dielectric constants and polarity indexes. The reaction resulted in an instantaneous formation of intensely purple coloured products with all the investigated TKIs. Spectrophotometric investigations confirmed that the reactions proceeded via the formation of charge-transfer complexes (CTC). The physical parameters (molar absorptivity, molar ratio, association constant and standard free energy) were determined for the CTC of all TKIs. Computational calculations for the relative electron densities on each atom of the TKI molecule and molecular modelling for the CTC were conducted, and the site(s) of interaction on each TKI molecule were determined. Under the optimized conditions, Beer's law correlating the absorbances of the CTC with the concentrations of TKIs were obeyed in the range of 5-500 µg/well with good correlation coefficients (0.9991-0.9998). The limits of detection and quantitation were in the ranges of 1.89-5.09 and 5.74-15.42 µg/well, respectively. The proposed MW-SPA showed high precisions as the values of the relative standard deviations did not exceed 2.01 and 2.45% for the intra- and inter-assay precision, respectively. The accuracy of MW-SPA was proved by recovery studies as the recovery values were in the range of 98.8-103.7%. The proposed MW-SPA was successfully applied for the determination of all TKIs in their bulk forms and pharmaceutical formulations (tablets) with good accuracy and precisions. The proposed MW-SPA is the first assay that can analyse all the TKIs on a single assay system without modifications in the detection wavelength. Additional advantages of the proposed MW-SPA are simple, economic, and more importantly have high throughput. Therefore, the assay can be helpful and beneficial for routine analysis of TKIs in their pharmaceutical formulations in quality control laboratories.


Subject(s)
Benzoquinones , Protein Kinase Inhibitors , Spectrophotometry , Drug Compounding
10.
Molecules ; 26(3)2021 Jan 31.
Article in English | MEDLINE | ID: mdl-33572664

ABSTRACT

The tyrosine kinase inhibitors (TKIs) are chemotherapeutic drugs used for the targeted therapy of various types of cancer. This work discusses the experimental and computational evaluation of chloranilic acid (CLA) as a universal chromogenic reagent for developing a novel 96-microwell spectrophotometric assay (MW-SPA) for TKIs. The reaction resulted in an instantaneous formation of intensely purple colored products with TKIs. Spectrophotometric results confirmed that the reactions proceeded via the formation of charge-transfer complexes (CTCs). The physical parameters were determined for the CTCs of all TKIs. Computational calculations and molecular modelling for the CTCs were conducted, and the site(s) of interaction on each TKI molecule were determined. Under the optimized conditions, Beer's law correlating the absorbances of the CTCs with the concentrations of TKIs were obeyed in the range of 10-500 µg/well with good correlation coefficients (0.9993-0.9998). The proposed MW-SPA fully validated and successfully applied for the determination of all TKIs in their bulk forms and pharmaceutical formulations (tablets). The proposed MW-SPA is the first assay that can analyze all the TKIs on a single assay system without modifications in the detection wavelength. The advantages of the proposed MW-SPA are simple, economic and, more importantly, have high throughput.


Subject(s)
Benzoquinones/pharmacology , Models, Molecular , Protein Kinase Inhibitors/pharmacology , Protein-Tyrosine Kinases/antagonists & inhibitors , Benzoquinones/chemistry , Drug Design , Molecular Conformation , Protein Kinase Inhibitors/chemistry , Spectrophotometry , Thermodynamics
11.
Antibiotics (Basel) ; 9(3)2020 Mar 23.
Article in English | MEDLINE | ID: mdl-32210014

ABSTRACT

Delafloxacin (DLX) is a recently-approved fluoroquinolone antibiotic, which is recommended for the treatment of "acute bacterial skin and skin structure infections". A thorough literature survey revealed only a single published method for the estimation of DLX using UPLC-MS/MS technique in biological samples. There is no high-performance thin-layer chromatography (HPTLC) method has been reported for the estimation of DLX in dosage forms and/or biological samples. Therefore, a selective, sensitive, rapid and validated HPTLC-densitometry technique has been used for the estimation of DLX in human plasma for the first time. HPTLC quantification of DLX and internal standard (IS; gatifloxacin) was carried out on glass coated silica gel 60 F254 HPTLC plates using the ternary mixture of ethyl acetate:methanol:ammonia solution 5:4:2 (%, v/v/v) as the mobile phase. Densitometric detection was done at 344 nm. The Rf values were recorded as 0.43 and 0.27 for the DLX and the IS, respectively. The linearity range of DLX was obtained as 16-400 ng/band. A simple protein precipitation method was used for the extraction of analyte from plasma using methanol. The proposed HPTLC technique was validated for "linearity, accuracy, precision, and robustness". The proposed HPTLC technique was successfully utilized for the assessment of pharmacokinetic profile of DLX in rats after oral administration. After oral administration, the peak plasma concentration of DLX was obtained as 194.19 ng/ml in 1 h. The proposed HPTLC method could be applied in study of pharmacokinetic profile and therapeutic drug monitoring of DLX in clinical practice.

12.
Article in English | MEDLINE | ID: mdl-32164966

ABSTRACT

Isotretinoin is chemically named as: (2Z, 4E, 6E, 8E)-3,7-Dimethyl-9-(2,6,6-trimethylcyclohex-1-enyl)nona-2,4,6,8-tetraenoic acid. It is an orally active retinoic acid derivative for the treatment of severe refractory nodulocystic acne. It acts primarily by reducing sebaceous gland size and sebum production, and as a result alters skin surface lipid composition. Using isotretinoin for 1-2mg/kg/day for 3-4 months produces 60%-95% clearance of inflammatory lesions in patients with acne. Doses as low as 0.1mg/kg/day have also proven successful in the clearance of lesions. Encouraging results have also been seen in small numbers of patients with rosacea, Side effects affecting the mucocutaneous system and raised serum triglyceride levels occur in most patients receiving isotretinoin. Isotretinoin is strictly contraindicated in women of childbearing potential. This profile discusses and explains names of isotretinoin, its physical and chemical characteristics. It also includes methods of preparation, thermal and spectral behavior, methods of analysis, and pharmacology.


Subject(s)
Isotretinoin/pharmacology , Sebaceous Glands/drug effects , Acne Vulgaris/drug therapy , Contraindications, Drug , Female , Humans , Sebum , Tretinoin
13.
Article in English | MEDLINE | ID: mdl-32164967

ABSTRACT

Meloxicam, an oxicam derivative: 4-Hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2- benzothiazine-3-carboxamide 1,1-dioxide, is a nonsteroidal anti-inflammatory drug (NSAID). It is a selective inhibitor of cyclooxygenase-2 (COX-2). It is used in the management of rheumatoid arthritis, acute exacerbations of osteoarthritis, ankylosing spondylitis and juvenile idiopathic arthritis. It is given in a single oral dose of 7.5mg, increased if necessary to a maximum of 15mg daily (7.5mg in the elderly). It may also be given by rectal suppository in doses similar to those used orally. The reported side effects of meloxicam are similar to those of nonsteroidal anti-inflammatory drugs (NSAIDs), such as abdominal pain, anemia, and edema. There is also an increased risk of serious gastrointestinal (GI) adverse events, including ulceration and bleeding. This profile is prepared to discuss and explain physical characteristics, Proprietary and nonproprietary names of meloxicam. It also includes methods of preparation, thermal and spectral behavior, methods of analysis, pharmacokinetics, metabolism, excretion and pharmacology.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Meloxicam/pharmacology , Aged , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Arthritis/classification , Arthritis/drug therapy , Humans , Meloxicam/adverse effects , Thiazines , Thiazoles
14.
Article in English | MEDLINE | ID: mdl-31029221

ABSTRACT

Thiouracil, 2-sulfanylidene-1H-pyrimidin-4-one, has been used as anti-thyroid, coronary vasodilator, and in congestive heart failure. It was found to cause agranulocytosis and it is suspected to be teratogenic and carcinogenic. Owing to its high frequency of adverse reactions, especially agranulocytosis, its use was abandoned in favor of other, less toxic drugs, such as propylthiouracil and methimazole. Thiouracil refers both to a specific molecule consisting of a sulfated uracil and a family of molecules based upon the structure. An important member of this family is propylthiouracil, which is a thiourea antithyroid drug that acts by blocking the production of thyroid hormones; it also inhibits the peripheral deiodination of thyroxine to tri-iodothyronine. This profile is prepared to discuss and explain physical and chemical properties, proprietary and nonproprietary names of thiouracil and propylthiouracil. It also includes uses and applications, methods of preparation, thermal and spectral behavior and methods of analysis. In addition, metabolism, excretion and pharmacology of propylthiouracil are also discussed.


Subject(s)
Antithyroid Agents/pharmacology , Thiouracil/pharmacology , Antithyroid Agents/chemistry , Methimazole , Propylthiouracil , Thiouracil/chemistry , Thyroxine
15.
Article in English | MEDLINE | ID: mdl-31029222

ABSTRACT

Topiramate, 2,3:4,5-di-O-isopropylidene-ß-d-fructopyranose sulfamate, is a potent antiepileptic drug with a broad spectrum of activity. It is effective in both partial and generalized seizures. Topiramate was also found to have significant efficacy in migraine prevention with considerable reductions in the frequency of migraine headaches. The most common adverse events, which may accompany the use of topiramate, are paresthesia, fatigue, decreased appetite, nausea, diarrhea, weight decrease and taste perversion. The weight loss observed with the use of topiramate in obese, epileptic patients, afforded the approval of this drug as an anti-obesity medication. This action is thought to be based on the selective inhibition of mitochondrial carbonic anhydrase isoforms. This profile is prepared to discuss and explain physical characteristics, proprietary and nonproprietary names of topiramate. It also includes methods of preparation, thermal and spectral behavior and methods of analysis. Pharmacokinetics, metabolism, excretion and pharmacology together with its uses and applications are also discussed.


Subject(s)
Anticonvulsants/pharmacology , Topiramate/pharmacology , Anticonvulsants/chemistry , Epilepsy/drug therapy , Humans , Migraine Disorders/drug therapy , Topiramate/chemistry
16.
J Anal Toxicol ; 43(3): 203-211, 2019 Apr 01.
Article in English | MEDLINE | ID: mdl-30295849

ABSTRACT

Suvorexant (SVR), lorcaserin (LCR) and brivaracetam (BVR) have been recently approved for the treatment of insomnia, obesity and epilepsy, respectively. Despite their clinical uses, these drugs have some abuse potential and have been enlisted under the schedule IV (SVR, LVR) and schedule V (BVR) categories of the Controlled Substances Act. A sensitive UPLC-MS-MS assay was developed for simultaneously determining SVR, LCR and BVR in human plasma. The liquid-liquid extraction method, using tert-butyl methyl ether as an extracting solvent, was used for sample preparation. Chromatographic separation was performed by using the Acquity BEH C18 column, using 10 mM ammonium acetate/acetonitrile/formic acid (15/85/0.1%; v/v/v) as the mobile phase. For sample ionization, electrospray ionization was used in the positive-ion mode. The multiple-reaction monitoring mode was used for detecting and quantifying analytes by using separate precursor-to-product ion transitions. The assay was validated following the SWGTOX guidelines, and all validation results were within the acceptable limits. The calibration curves of the analytes in the plasma were found to be linear, and the coefficient of determination (R2) was ≥ 0.992 for all the three analytes. The limit of detection values for SVR, LCR and BVR were 0.08, 0.11 and 0.26 ng/mL, respectively, whereas the limit of quantification values were 0.16, 0.27 and 0.65 ng/mL, respectively. The assay developed in this study is suitable for the identification and quantification of SVR, LCR and BVR in the forensic laboratory.


Subject(s)
Azepines/blood , Benzazepines/blood , Pyrrolidinones/blood , Substance Abuse Detection/methods , Substance-Related Disorders/blood , Triazoles/blood , Calibration , Chromatography, High Pressure Liquid , Humans , Limit of Detection , Liquid-Liquid Extraction , Prescription Drugs , Reference Standards , Reproducibility of Results , Substance Abuse Detection/instrumentation , Tandem Mass Spectrometry
17.
J Pharm Biomed Anal ; 164: 1-8, 2019 Feb 05.
Article in English | MEDLINE | ID: mdl-30339947

ABSTRACT

Suvorexant is a novel sedative/hypnotic drug approved for treatment of insomnia. It has significant forensic importance due to its hypnotic and depressant effects on central nervous system. In this study, a highly sensitive UPLC-MS/MS assay was developed and validated for the determination of suvorexant in urine sample. A simplified dispersive liquid-liquid microextraction followed by ultrasound assisted back extraction from solidified floating organic droplets was employed for sample preparation. The 20 µL of 1-undecanol and 200 µL of acetonitrile were used as extraction solvent and dispersive solvent, respectively. An ultrasound assisted back extraction step was employed to enable the cleanup procedure compatible with mass spectrometric detection. Acquity CSH™C18 column with mobile phase composition of 15 mM ammonium acetate: acetonitrile: formic acid (15:85:0.1%; v/v/v) were used for chromatographic separation. The multiple reaction monitoring transition of 451.12 →104.01 and 451.12→186.04 were used for identification and quantification of suvorexant, respectively, whereas 237.06→194.1 was used for IS in positive mode. The assay demonstrated good linearity in the range of 0.27-1000 ng mL-1 with limit of detection (LOD) and quantification (LOQ) of 0.10 and 0.27 ng mL-1, respectively. Assay validation was performed by following SWGTOX guidelines and all validation results were found to be within acceptable limits. This is the first report of dispersive liquid-liquid microextraction based on solidification of floating organic droplets employed to UPLC-MS/MS for application in biological fluids.


Subject(s)
Azepines/urine , Liquid Phase Microextraction/methods , Sleep Aids, Pharmaceutical/urine , Triazoles/urine , Chromatography, High Pressure Liquid/instrumentation , Chromatography, High Pressure Liquid/methods , Healthy Volunteers , Humans , Limit of Detection , Solvents/chemistry , Tandem Mass Spectrometry/instrumentation , Tandem Mass Spectrometry/methods , Ultrasonic Waves
18.
Article in English | MEDLINE | ID: mdl-28431781

ABSTRACT

Clenbuterol (Broncodil and trade) is a direct-acting sympathomimetic agent with mainly beta-adrenergic activity and a selective action on ß2 receptors (a ß2 agonist). It has properties similar to those of salbutamol. It is used as a bronchodilator in the management of reversible airways obstruction, as in asthma and in certain patients with chronic obstructive pulmonary disease. The uses, applications, and the synthetic pathways of this drug are outlined. Physical characteristics including: ionization constant, solubility, X-ray powder diffraction pattern, thermal methods of analysis, UV spectrum, IR spectrum, mass spectrum are all produced. This profile also includes the monograph of British Pharmacopoeia, together with several reported analytical methods including spectrophotometric, electrochemical, chromatographic, immunochemical methods, and capillary electrophoretic methods. The stability, the pharmacokinetic behavior, and the pharmacology of the drug are also provided.


Subject(s)
Clenbuterol , Adrenergic beta-Agonists/chemistry , Adrenergic beta-Agonists/pharmacokinetics , Adrenergic beta-Agonists/pharmacology , Adrenergic beta-Agonists/therapeutic use , Animals , Asthma/drug therapy , Bronchodilator Agents/chemistry , Bronchodilator Agents/pharmacokinetics , Bronchodilator Agents/pharmacology , Bronchodilator Agents/therapeutic use , Clenbuterol/chemistry , Clenbuterol/pharmacokinetics , Clenbuterol/pharmacology , Clenbuterol/therapeutic use , Humans , Molecular Structure , Pulmonary Disease, Chronic Obstructive/drug therapy , Sympathomimetics/chemistry , Sympathomimetics/pharmacokinetics , Sympathomimetics/pharmacology , Sympathomimetics/therapeutic use
19.
J Anal Toxicol ; 41(2): 114-120, 2017 Mar 01.
Article in English | MEDLINE | ID: mdl-28376227

ABSTRACT

Suvorexant is a dual orexin receptor antagonist, recently approved by USFDA for the treatment of insomnia. It is drug-of-abuse and listed in Schedule IV drug of the Controlled Substances Act. In this study, a simple and highly sensitive UPLC-MS/MS assay was developed and fully validated for the determination of suvorexant in rat plasma. Both suvorexant and internal standard (rivaroxaban; IS) were separated on Aquity BEHTM C18 column after the extraction form plasma using diethyl ether as extracting agent. An isocratic mobile phase, consisting of acetonitrile and 10 mM ammonium acetate in composition ratio of 85:15 was eluted at flow rate of 0.3 mL/min. Both suvorexant and IS were eluted within one min with total run time of 1.5 min only. The ionization was performed on electrospray ionization interface in positive mode by multiple reaction monitoring. Precursor to product ion transition of 451.12 > 104.01 for qualifier and 451.12 > 186.04 for quantifier were used for suvorexant whereas 436.10 > 144.93 for IS, respectively. The calibration curves in plasma were linear in the concentration range of 0.33-200 ng/mL (r2 ≥ 0.995) having limit of detection and limit of quantification of 0.10 and 0.33 ng/mL, respectively. All the validation parameters results were found to be within the acceptable limits according to the "Scientific Working Group for Forensic Toxicology (SWGTOX) guidelines" and can be implemented for forensic analysis.


Subject(s)
Azepines/blood , Chromatography, Liquid/methods , Illicit Drugs/blood , Sleep Aids, Pharmaceutical/blood , Spectrometry, Mass, Electrospray Ionization/methods , Tandem Mass Spectrometry/methods , Triazoles/blood , Animals , Limit of Detection , Male , Rats , Rats, Wistar , Reproducibility of Results
20.
Article in English | MEDLINE | ID: mdl-26051686

ABSTRACT

Losartan (Cozaar™) is an angiotensin II receptor antagonist with antihypertensive activity. It is used in the management of hypertension and heart failure. Nomenclature, formulae, elemental analysis, and appearance of the drug are included in this review. The uses, applications, and the variety of synthetic pathways of this drug are outlined. Physical characteristics including: ionization constant, solubility, X-ray powder diffraction pattern, thermal methods of analysis, UV spectrum, IR spectrum, mass spectrum with fragmentation patterns, and NMR (1H and 13C) spectra of losartan together with the corresponding figures and/or tables are all produced. This profile also includes the monograph of British Pharmacopoeia, together with several reported analytical methods including: spectrophotometric, electrochemical, chromatographic, and capillary electrophoretic methods. The stability, the pharmacokinetic behavior and the pharmacology of the drug are also provided.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/chemistry , Antihypertensive Agents/chemistry , Losartan/chemistry , Angiotensin II Type 1 Receptor Blockers/pharmacokinetics , Angiotensin II Type 1 Receptor Blockers/pharmacology , Animals , Antihypertensive Agents/pharmacokinetics , Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Chemistry, Pharmaceutical , Drug Stability , Humans , Hypertension/drug therapy , Hypertension/physiopathology , Losartan/pharmacokinetics , Losartan/pharmacology , Molecular Structure , Technology, Pharmaceutical/methods
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