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1.
J Pharm Biomed Anal ; 248: 116282, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38870835

ABSTRACT

Cabergoline is a dopamine agonist with applications as anti-Parkinson drug and prolactin inhibitor. The cabergoline drug product Laktostop® 50 µg/mL is used in veterinary medicine for lactation suppression in cats and dogs e.g. during false pregnancy. Recently, during ongoing HPLC stability testing of Laktostop® 50 µg/mL a new oxidation product of Cabergoline was identified. A synthesis starting from Cabergoline was developed, followed by full characterization of the unknown impurity. Preliminary HPLC and LC-MS analyses indicated the unknown impurity as mono-oxygenated product of Cabergoline (Cabergoline N-oxide) that is presumably formed with oxygen by a radical mechanism. Thus, Cabergoline was treated with oxidizing agents such as m-chloroperoxybenzoic acid to afford the desired Cabergoline-N-oxide as a byproduct. After isolation by column chromatography, NMR and LC-MS-MS studies provided evidence that oxidation occurred at the N-allyl nitrogen of Cabergoline to form Cabergoline-N-oxide. © 1905 Elsevier Science. All rights reserved.


Subject(s)
Cabergoline , Drug Stability , Ergolines , Oxidation-Reduction , Tandem Mass Spectrometry , Cabergoline/chemistry , Chromatography, High Pressure Liquid/methods , Ergolines/chemistry , Ergolines/analysis , Tandem Mass Spectrometry/methods , Magnetic Resonance Spectroscopy/methods , Dopamine Agonists/chemistry , Dopamine Agonists/analysis , Drug Contamination , Chromatography, Liquid/methods
2.
Aging (Albany NY) ; 13(12): 16620-16636, 2021 06 25.
Article in English | MEDLINE | ID: mdl-34170848

ABSTRACT

Dopamine receptor, a polypeptide chain composed of 7 hydrophobic transmembrane regions, is a new and vital drug target, especially Dopamine receptor 2(D2). Targeting dopamine receptors, Dopamine receptor agonists are a class of drugs similar in function and structure to dopamine and can directly act on dopamine receptors and activate it. Clinically, Dopamine receptor agonist drugs have achieved significant therapeutic effects on prolactinoma and Parkinson's Disease. In the study, we virtually screened a series of potential effective agonists of Dopamine receptor by computer techniques. Firstly, we used the Molecular Docking (LibDock) step to screen out some molecules that can dock well with the protein. Then, analysis of toxicity prediction and ADME (adsorption, distribution, metabolism and excretion) were carried out. More precise molecular docking (CDOCKER) and 3-Dimensional Quantitative Structure-Activity Relationship Modeling Study(3D-QSAR) pharmacophore generation were implemented to research and explore these compounds' binding mechanism with Dopamine receptor. Last but not least, to assess compound's binding stabilities, we carried out a molecular dynamic analysis. As the results show, two compounds (ZINC000008860530 and ZINC000004096987) from the small molecule database (ZINC database) were potential effective agonists of Dopamine receptor. These two compounds can combine with Dopamine receptor with higher affinity and proved to be no toxic. The cell experiment showed that two compounds could inhibit the proliferation and PRL secretion of MMQ cells (pituitary tumor cells). Thus, this study provided valuable information about Dopamine receptor agonist-based drug discovery. So, this study will benefit patients with prolactinoma and Parkinson's disease a lot.


Subject(s)
Biological Products/chemistry , Biological Products/pharmacology , Dopamine Agonists/chemistry , Dopamine Agonists/pharmacology , Molecular Docking Simulation , Receptors, Dopamine/chemistry , Biological Products/analysis , Biological Products/toxicity , Bromocriptine/chemistry , Bromocriptine/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Dopamine Agonists/analysis , Dopamine Agonists/toxicity , Drug Evaluation, Preclinical , Humans , Hydrogen Bonding , Ligands , Molecular Dynamics Simulation , Prolactin/metabolism
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 207: 143-149, 2019 Jan 15.
Article in English | MEDLINE | ID: mdl-30223248

ABSTRACT

Currently, trace detection of drugs, medicinal products, psychoactive substances, poisons and other natural or synthetic compounds in the human body has become one of the most important areas of interest in medicine, toxicology and forensic research. Due to the rapid development of nanotechnology, applications in forensic and biological sciences, food industry and art preservation there is an increasing interest in surface-enhanced Raman scattering (SERS) spectroscopy as a technique capable of low detection limits in the analysis of small amounts of studied analytes. In this study, different excitation wavelengths (785 nm and 1064 nm) were used to find the appropriate experimental conditions for the detection and identification of medically significant alkaloids - atropine and pergolide - by means of surface-enhanced Raman scattering spectroscopy. SERS spectra of selected alkaloids were measured in the concentration range 10-3-10-9 mol∙L-1 using large-scaled platinum substrates coated with electrochemically prepared gold or silver SERS-active layers. Identification was based on the assignment of surface-enhanced characteristic vibrational bands using theoretical (DFT) calculations and comparing them with normal (non-enhanced) Raman spectra of pure compounds. All sets of spectral data were subjected to multivariate statistical approach (partial least squares regression) aiming at prediction of alkaloids concentration in developed models and its comparison with experimental results.


Subject(s)
Adjuvants, Anesthesia/analysis , Atropine/analysis , Dopamine Agonists/analysis , Pergolide/analysis , Spectrum Analysis, Raman/methods , Gold/chemistry , Least-Squares Analysis , Silver/chemistry
4.
Colloids Surf B Biointerfaces ; 174: 174-180, 2019 Feb 01.
Article in English | MEDLINE | ID: mdl-30453136

ABSTRACT

The present work reports the processing of laser irradiated Si arrays (LISi) and underlines their surface enhanced Raman scattering (SERS) functionality. A nanostructured Si/SiOx surface forms providing additional fluidic and photoprotective properties. Because of their optical and surface characteristics, the arrays exhibit a SERS analytical enhancing factor of 500, without any noble metals such as gold or silver. Micro-Raman maps allowed studying LISi properties, identifying maximum amplification in nanostructured areas characterized by the presence of 7 nm Si nanocrystals. These structures are confined by a SiOx layer as illustrated by XPS valence band measurements. The highly hydrophilic LISi areas allow a pre-concentration of target molecules prior to SERS analysis. A relevant application of LISi was found in the detection of apomorphine (APO), a drug used for the treatment of Parkinson's disease. In contrast with what is obtained by using gold SERS substrates, LISi allows the detection of APO with no sign of oxidation. This invites for the use of the Si/SiOx SERS detection in future systems for the personalized delivery of APO.


Subject(s)
Apomorphine/analysis , Dopamine Agonists/analysis , Lasers , Nanostructures/chemistry , Silicon/chemistry , Apomorphine/pharmacology , Dopamine Agonists/pharmacology , Oxidation-Reduction , Particle Size , Receptors, Dopamine/metabolism , Spectrum Analysis, Raman , Surface Properties
5.
Food Chem ; 276: 745-753, 2019 Mar 15.
Article in English | MEDLINE | ID: mdl-30409657

ABSTRACT

The phenethylamine alkaloid hordenine, present in germinated barley, was identified recently as a functionally selective dopamine D2 receptor agonist contributing potentially to the rewarding effects of drinking beer. Here, it was shown that the hordenine precursor N-methyltyramine binds with a similar affinity to the dopamine D2 receptor as hordenine (Ki 31.3 µM) showing also selectivity towards the G protein-mediated pathway over the ß-arrestin pathway. Using a newly developed UHPLC-ESI-MS/MS method to monitor beer production, we demonstrated that hordenine and N-methyltyramine were released continuously from barley malt during mashing and were stable during fermentation and conditioning. The amounts released from different base malt types were in a similar range but tended to be higher from caramel malts. Hordenine and N-methyltyramine concentrations in 24 types of beer varied between 1.05-6.32 and 0.59-4.61 mg/L, respectively. Thus, the human uptake of the alkaloids during beer consumption is in the low milligram range.


Subject(s)
Beer/analysis , Dopamine Agonists/analysis , Tyramine/analogs & derivatives , Animals , CHO Cells , Chromatography, High Pressure Liquid , Cricetulus , Dopamine Agonists/metabolism , Fermentation , Food Analysis/methods , Hordeum/metabolism , Humans , Radioligand Assay , Receptors, Dopamine D2/agonists , Receptors, Dopamine D2/genetics , Receptors, Dopamine D2/metabolism , Spectrometry, Mass, Electrospray Ionization , Tandem Mass Spectrometry , Tyramine/analysis , Tyramine/metabolism
6.
J Psychoactive Drugs ; 49(3): 175-181, 2017.
Article in English | MEDLINE | ID: mdl-28266899

ABSTRACT

The blue lotus flower (Nymphea caerulea) is an Egyptian water lily containing apomorphine and nuciferine. Apomorphine has been described as a psychoactive alkaloid and is a non-selective dopamine agonist primarily used to treat Parkinson's disease as it stimulates dopamine receptors and improves motor function. Nuciferine is an alkaloid associated with dopamine receptor blockade. Today, blue lotus flower is used as a sleep aid and anxiety reliever. The rebuildable dripping atomizer (RDA) is an electronic cigarette that allows direct application of an e-liquid onto the coil in the atomizer for aerosolization, compared to a typical electronic cigarette where the e-liquid is wicked from a storage vessel to the coil. Our laboratory received a dark-brown resin material from a concerned parent. The resin had been confiscated from an adolescent who had a reported history of marijuana use. The resin was later identified as blue lotus flower (N. caerulea). This resin, together with four commercially available blue lotus products, was analyzed for content. Apomorphine was detected in two samples, and nuciferine was detected in all five samples. The confiscated resin was determined to contain no apomorphine and 4300 ng/g of nuciferine. The nuciferine resin was shown to aerosolize using aRDA electric cigarette.


Subject(s)
Aporphines/analysis , Electronic Nicotine Delivery Systems , Nebulizers and Vaporizers , Nymphaea , Resins, Plant/analysis , Apomorphine/analysis , Dopamine Agonists/analysis , Humans
7.
Anal Chem ; 88(12): 6492-9, 2016 06 21.
Article in English | MEDLINE | ID: mdl-27212615

ABSTRACT

Microiontophoresis uses an electric current to eject a drug solution from a glass capillary and is often utilized for targeted delivery in neurochemical investigations. The amount of drug ejected, and its effective concentration at the tip, has historically been difficult to determine, which has precluded its use in quantitative studies. To address this, a method called controlled iontophoresis was developed which employs a carbon-fiber microelectrode incorporated into a multibarreled iontophoretic probe to detect the ejection of electroactive species. Here, we evaluate the accuracy of this method. To do this, we eject different concentrations of quinpirole, a D2 receptor agonist, into a brain slice containing the dorsal striatum, a brain region with a high density of dopamine terminals. Local electrical stimulation was used to evoke dopamine release, and inhibitory actions of quinpirole on this release were examined. The amount of drug ejected was estimated by detection of a coejected electrochemical marker. Dose response curves generated in this manner were compared to curves generated by conventional perfusion of quinpirole through the slice. We find several experimental conditions must be optimized for accurate results. First, selection of a marker with an identical charge was necessary to mimic the ejection of the cationic agonist. Next, evoked responses were more precise following longer periods between the end of the ejection and stimulation. Lastly, the accuracy of concentration evaluations was improved by longer ejections. Incorporation of these factors into existing protocols allows for greater certainty of concentrations delivered by controlled iontophoresis.


Subject(s)
Dopamine Agonists/administration & dosage , Drug Delivery Systems/methods , Iontophoresis/methods , Quinpirole/administration & dosage , Receptors, Dopamine D2/agonists , Animals , Brain/metabolism , Corpus Striatum/metabolism , Dopamine Agonists/analysis , Dopamine Agonists/pharmacokinetics , Male , Quinpirole/analysis , Quinpirole/pharmacokinetics , Rats, Sprague-Dawley
8.
Article in English | MEDLINE | ID: mdl-25813902

ABSTRACT

Usually, insufficient intratumoral concentration of therapeutic drugs is one of the reasons for tumor treatment failure. However, little is known about intratumoral distribution of bromocriptine in non-responding prolactinomas because of extremely low drug concentration and small prolactinoma tissue samples. In this study, a sensitive, rapid and high-throughput quantitative bioanalytical method has been established by using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for the determination of bromocriptine at trace level in human prolactinoma tissue. As little as 20 mg (wet weight) tissue sample was required and total analysis time was 6 min in this method. The assay quantifies over a linear range of 50 fg/mg to 5 pg/mg, and has a 25 fg/mg limit of detection at a signal/noise ratio of 3. This validated method was successfully used to quantitatively determine bromocriptine in clinical post-operative bromocriptine-sensitive and -resistant prolactinomas. The results revealed bromocriptine concentration in resistant prolactinomas (0.49-1.25 pg/mg) was significantly higher than that in sensitive prolactinomas (0.057-0.47 pg/mg). These results provided direct evidence to demonstrate the reseaon for failure of bromocriptine treatment in some patients with prolactinoma was "intrinsic" tumor (cell) resistence, rather than insufficient drug concentration in tumor tissue. Additionaly, this HPLC-MS/MS method has been shown to be suitable for bromocriptine analysis in small amount tissue sample and could be adapted for therapeutic drug monitoring of other clinical medicine.


Subject(s)
Bromocriptine/analysis , Chromatography, High Pressure Liquid/methods , Dopamine Agonists/analysis , Drug Monitoring/methods , Pituitary Neoplasms/drug therapy , Prolactinoma/drug therapy , Tandem Mass Spectrometry/methods , Bromocriptine/administration & dosage , Dopamine Agonists/administration & dosage , Humans , Pituitary Neoplasms/chemistry , Prolactinoma/chemistry , Sensitivity and Specificity
9.
J Forensic Leg Med ; 21: 48-52, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24365689

ABSTRACT

Cocaine is a well known trigger of acute coronary syndromes. Over the last 10 years levamisole, a veterinary anthelminthic drug has been increasingly used as an adulterant of cocaine. Levamisole was used to treat pediatric nephritic syndrome and rheumatoid arthritis before being withdrawn from the market due to its significant toxicity, i.e. hematological complications and vasculitis. The major complications of levamisole-adultered cocaine reported up to now are hematological and dermatological. The case reported here is of a 25 year old man with a history of cocaine abuse who died at home after complaining of retrosternal pain. Postmortem CT-angiography, autopsy, and chemical and toxicological analyses were performed. An eroded coronary artery plaque was found at the proximal segment of the left anterior descending coronary artery. Two myocardial infarct scars were present in the left ventricle. Microscopic examination of the coronary artery revealed infiltration of eosinophils into the adventitia and intima. Toxicological examination confirmed the presence of cocaine and its metabolites in the peripheral blood, and of levamisole in the urine and pericardial fluid. Eosinophilic inflammatory coronary artery pathologies have been clinically linked to coronary dissection, hypersensitivity coronary syndrome and vasospastic allergic angina. The coronary pathology in the presented case could be a complication of levamisole-adultered cocaine use, in which an allergic or immune-mediated mechanism might play a role. The rise in cocaine addiction worldwide and the increase of levamisole adulterated cocaine highlights the importance of updating our knowledge of the effects of adultered cocaine abuse.


Subject(s)
Acute Coronary Syndrome/chemically induced , Cocaine-Related Disorders/complications , Death, Sudden/etiology , Dopamine Agonists/adverse effects , Drug Contamination , Levamisole/adverse effects , Acute Coronary Syndrome/pathology , Adult , Cocaine/blood , Cocaine/chemistry , Coronary Vessels/pathology , Dopamine Agonists/analysis , Eosinophils/pathology , Humans , Levamisole/analysis , Male , Myocardium/pathology , Narcotics/blood , Narcotics/chemistry , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Plaque, Atherosclerotic/pathology , Troponin I/blood , Tryptases/blood
10.
Article in English | MEDLINE | ID: mdl-23423476

ABSTRACT

The nucleus accumbens (NAc) is a critical brain region involved in many reward-related behaviors. The NAc comprises major compartments the core and the shell, which encompass several subterritories. GABAergic medium-sized spiny neurons (MSNs) constitute the output neurons of the NAc core and shell. While the functional organization of the NAc core outputs resembles the one described for the dorsal striatum, a simple classification of the NAc shell neurons has been difficult to define due to the complexity of the compartmental segregation of cells. We used a variety of BAC transgenic mice expressing enhanced green fluorescence (EGFP) or the Cre-recombinase (Cre) under the control of the promoter of dopamine D1, D2, and D3 receptors and of adenosine A2a receptor to dissect the microanatomy of the NAc. Moreover, using various immunological markers we characterized in detail the distribution of MSNs in the mouse NAc. In addition, cell-type specific extracellular signal-regulated kinase (ERK) phosphorylation in the NAc subterritories was analyzed following acute administration of SKF81297 (a D1R-like agonist), quinpirole (a D2 receptors (D2R)-like agonist), apomorphine (a non-selective DA receptor agonist), raclopride (a D2R-like antagonist), and psychostimulant drugs, including cocaine and d-amphetamine. Each drug generated a unique topography and cell-type specific activation of ERK in the NAc. Our results show the existence of marked differences in the receptor expression pattern and functional activation of MSNs within the shell subterritories. This study emphasizes the anatomical and functional heterogeneity of the NAc, which will have to be considered in its further study.


Subject(s)
GABAergic Neurons/chemistry , GABAergic Neurons/metabolism , Nucleus Accumbens/chemistry , Nucleus Accumbens/metabolism , Animals , Dopamine Agonists/analysis , Dopamine Agonists/metabolism , GABAergic Neurons/cytology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Nucleus Accumbens/cytology , Receptors, Dopamine/chemistry , Receptors, Dopamine/metabolism
11.
J Clin Pharmacol ; 51(8): 1177-85, 2011 Aug.
Article in English | MEDLINE | ID: mdl-20959524

ABSTRACT

Dexpramipexole (KNS-760704; [6R]-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine) is a novel synthetic amino-benzothiazole in development for the treatment of amyotrophic lateral sclerosis (ALS). Preclinical studies have shown that dexpramipexole is neuroprotective in vitro and in vivo, is highly orally bioavailable and water soluble, and rapidly achieves and maintains high central nervous system concentrations relative to plasma. Two phase 1 clinical studies were conducted to assess the safety, tolerability, and pharmacokinetics (PK) of single and multiple doses of dexpramipexole in 54 healthy male and female adults. The effect of food on the single-dose PK of dexpramipexole was also evaluated. Single doses (50 mg, 150 mg, or 300 mg) and multiple doses (50 mg twice daily, 100 mg twice daily, or 150 mg twice daily) of dexpramipexole over 4.5 days were safe and well tolerated. Dexpramipexole was rapidly absorbed, with time to maximum plasma concentration ranging from 1.8 to 2.6 hours and half-life ranging from 6.4 to 8.1 hours under fasted conditions, and was mostly eliminated in urine as unchanged parent drug (84%-90% of dose). Food had no effect on the single-dose PK of dexpramipexole. These findings support the ongoing development of dexpramipexole for the treatment of ALS and further evaluation of the compound's therapeutic potential in other neurodegenerative diseases.


Subject(s)
Benzothiazoles/adverse effects , Benzothiazoles/pharmacokinetics , Dopamine Agonists/adverse effects , Dopamine Agonists/pharmacokinetics , Drugs, Investigational/adverse effects , Drugs, Investigational/pharmacokinetics , Adult , Benzothiazoles/administration & dosage , Benzothiazoles/analysis , Dopamine Agonists/administration & dosage , Dopamine Agonists/analysis , Dose-Response Relationship, Drug , Double-Blind Method , Drugs, Investigational/administration & dosage , Drugs, Investigational/analysis , Female , Food-Drug Interactions , Half-Life , Humans , Intestinal Absorption , Male , Metabolic Clearance Rate , Middle Aged , Plasma/chemistry , Pramipexole , Urine/chemistry
12.
Biomed Chromatogr ; 23(2): 212-8, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18814193

ABSTRACT

A highly sensitive and specific LC-MS/MS method has been developed and validated for the estimation of pramipexole (PPX) with 500 microL human plasma using memantine as an internal standard (IS). The API-4000 was operated under multiple-reaction monitoring mode (MRM) using the electrospray ionization technique. Solid-phase extraction was used to extract PPX and IS from human plasma. The resolution of peaks was achieved with 0.01 m ammonium acetate buffer (pH 4.4):acetonitrile (30:70, v/v) on a Discovery CN column. The total chromatographic run time was 3.0 min and the elution of PPX and IS occurred at approximately 2.32 and 2.52, respectively. The MS/MS ion transitions monitored were 212.10 --> 153.10 for PPX and 180.20 --> 107.30 for IS. The method was proved to be accurate and precise at linearity range of 20-3540 pg/mL with a correlation coefficient (r) of > or =0.999. The intra- and inter-day precision and accuracy values found to be within the assay variability limits as per the FDA guidelines. The developed assay method was applied to a pharmacokinetic study in human volunteers following oral administration of 0.25 mg PPX tablet.


Subject(s)
Benzothiazoles/analysis , Chromatography, Liquid/methods , Dopamine Agonists/analysis , Tandem Mass Spectrometry/methods , Benzothiazoles/administration & dosage , Benzothiazoles/pharmacokinetics , Dopamine Agonists/administration & dosage , Dopamine Agonists/pharmacokinetics , Drug Stability , Humans , Linear Models , Memantine/analysis , Pramipexole , Reference Standards , Reproducibility of Results , Sensitivity and Specificity , Solid Phase Extraction/methods , Spectrometry, Mass, Electrospray Ionization/methods
13.
Article in English | MEDLINE | ID: mdl-17719838

ABSTRACT

Three sensitive, selective, accurate spectrophotometric and spectrofluorimetric methods have been developed for the determination of ropinirole hydrochloride in tablets. The first method was based on measuring the absorbance of drug solution in methanol at 250 nm. The Beer's law was obeyed in the concentration range 2.5-24 microg ml(-1). The second method was based on the charge transfer reaction of drug, as n-electron donor with 7,7,8,8-tetracyanoquinodimethane (TCNQ), as pi-acceptor in acetonitrile to give radical anions that are measured at 842 nm. The Beer's law was obeyed in the concentration range 0.6-8 microg ml(-1). The third method was based on derivatization reaction with 4-chloro-7-nitrobenzofurazan (NBD-Cl) in borate buffer of pH 8.5 followed by measuring the fluorescence intensity at 525 nm with excitation at 464 nm in chloroform. Beer's law was obeyed in the concentration range 0.01-1.3 microg ml(-1). The derivatization reaction product of drug with NBD-Cl was characterized by IR, 1H NMR and mass spectroscopy. The developed methods were validated. The following analytical parameters were investigated: the molar absorptivity (epsilon), limit of detection (LOD, microg ml(-1)) and limit of quantitation (LOQ, microg ml(-1)), precision, accuracy, recovery, and Sandell's sensitivity. Selectivity was validated by subjecting stock solution of ropinirole to acidic, basic, oxidative, and thermal degradation. No interference was observed from common excipients present in formulations. The proposed methods were successfully applied for determination of drug in tablets. The results of these proposed methods were compared with each other statistically.


Subject(s)
Dopamine Agonists/analysis , Indoles/analysis , Spectrometry, Fluorescence/methods , Spectrophotometry/methods , Tablets/analysis , Acetonitriles/chemistry , Benzofurans/chemistry , Borates/chemistry , Buffers , Calibration , Chloroform/chemistry , Dopamine Agonists/chemistry , Hydrogen-Ion Concentration , Indoles/chemistry , Magnetic Resonance Spectroscopy , Mass Spectrometry , Methanol/chemistry , Molecular Structure , Nitriles/chemistry , Phosphates/chemistry , Reproducibility of Results , Sensitivity and Specificity
14.
Article in English | MEDLINE | ID: mdl-16979391

ABSTRACT

Rotigotine, an investigational dopamine agonist formulated as a patch, is being studied in Parkinson's disease. A microdialysis technique, in combination with microbore column liquid chromatography and electrochemical detection, was developed to monitor rotigotine levels in the brain. Microdialysis probes were inserted into the striata of anesthetized rats, and samples were collected during perfusion with Ringer's solution. Rotigotine was separated using a C18 reversed-phase column. The mobile phase consisted of 50mM Na(2)HPO(4) x 2H(2)O, 2.5 mM sodium octyl sulfonate, and pH 4.5; 35% volume to volume acetonitrile. The flow rate was 30 microl/min, and the potential of the glassy carbon electrode was set to +850 mV. The method allowed monitoring of the time course of brain extracellular rotigotine levels with a detection limit of 1 nM following either intravenous (0.5 mg/kg) or subcutaneous (5.0 mg/kg) rotigotine injection.


Subject(s)
Brain Chemistry , Chromatography, Liquid/methods , Dopamine Agonists/analysis , Tetrahydronaphthalenes/analysis , Thiophenes/analysis , Animals , Electrochemistry , Male , Microdialysis , Rats , Rats, Sprague-Dawley , Reproducibility of Results
15.
Rapid Commun Mass Spectrom ; 20(12): 1883-8, 2006.
Article in English | MEDLINE | ID: mdl-16715476

ABSTRACT

A sensitive, rapid and specific quantitative liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated for the determination of apomorphine (APO) in canine plasma. The analytes were prepared using one-step liquid-liquid extraction, and analyzed on a Waters Symmetry C(18) column interfaced with triple quadrupole tandem mass spectrometer. A mixture of methanol/0.1% formic acid in water (70: 30, v/v) was employed as the isocratic mobile phase. Positive electrospray ionization was utilized as the ionization source. The analyte and clenbuterol (internal standard) were both detected using multiple reaction monitoring (MRM) mode. The limit of detection (LOD) obtained was 0.03 ng/mL. The assay was linear over the concentration range of 0.1-100 ng/mL, and provided good precision (RSD) and good accuracy (RE). The analyte was stable by using antioxidants throughout the whole study. The experimental results show that LC/MS/MS is a rapid and sensitive method to analyze APO in plasma. Finally, the proposed method was successfully applied to a pharmacokinetic study of APO after intranasal administration of 0.5 mg apomorphine to 10 healthy beagle dogs.


Subject(s)
Apomorphine/analysis , Chromatography, High Pressure Liquid/methods , Dopamine Agonists/analysis , Spectrometry, Mass, Electrospray Ionization/methods , Tandem Mass Spectrometry/methods , Administration, Intranasal , Animals , Apomorphine/pharmacokinetics , Dogs , Dopamine Agonists/pharmacokinetics , Reproducibility of Results , Sensitivity and Specificity
16.
J Pharm Biomed Anal ; 41(4): 1152-6, 2006 Jun 16.
Article in English | MEDLINE | ID: mdl-16580170

ABSTRACT

A chiral liquid chromatographic method was developed for the enantiomeric resolution of Pramipexole dihydrochloride monohydrate, (S)-2-amino-4,5,6,7-tetra-hydro-6-(propylamino) benzothiazole dihydrochloride monohydrate, a dopamine agonist in bulk drugs. The enantiomers of Pramipexole dihydrochloride monohydrate were resolved on a Chiralpak AD (250 mm x 4.6 mm, 10 microm) column using a mobile phase system containing n-hexane:ethanol:diethylamine (70:30:0.1, v/v/v). The resolution between the enantiomers was found not less than eight. The presence of diethylamine in the mobile phase has played an important role in enhancing chromatographic efficiency and resolution between the enantiomers. The developed method was extensively validated and proved to be robust. The limit of detection and limit of quantification of (R)-enantiomer were found to be 300 and 900 ng/ml, respectively for 20 microl injection volume. The percentage recovery of (R)-enantiomer was ranged from 97.3 to 102.0 in bulk drug samples of Pramipexole dihydrochloride monohydrate. Pramipexole dihydrochloride monohydrate sample solution and mobile phase were found to be stable for at least 48 h. The proposed method was found to be suitable and accurate for the quantitative determination of (R)-enantiomer in bulk drugs.


Subject(s)
Antiparkinson Agents/analysis , Chromatography, Liquid/methods , Dopamine Agonists/analysis , Thiazoles/analysis , Benzothiazoles , Pramipexole , Reproducibility of Results , Stereoisomerism
17.
J Pharm Biomed Anal ; 38(4): 624-32, 2005 Jul 15.
Article in English | MEDLINE | ID: mdl-15967290

ABSTRACT

A new carbon paste electrode selective for piribedil (PD) was prepared and fully characterized in terms of composition, usable pH range, response time and thermal stability. The electrode active recognition is by liquid ion-exchange mechanism via the use of piribedil phosphomolybdate as ion-exchanger dissolved in tricresyl phosphate as a more suitable solvent mediator for the paste. The modified electrode showed a Nernstian slope of 58.4+/-0.6 mV over the concentration range of 7.5 x 10(-7) to 1 x 10(-3)M with an average recovery of 98.3-101.0% and R.S.D. of 0.45-1.31%. The electrode exhibits good selectivity for PD with respect to a large number of inorganic cations, organic cations, sugars and amino acids. The developed electrode was successfully used for the potentiometric determination of PD in its aqueous solutions, pharmaceutical preparation, and urine in batch and flow injection analysis (FIA).


Subject(s)
Dopamine Agonists/analysis , Piribedil/analysis , Algorithms , Calibration , Carbon , Chromatography, Ion Exchange , Dopamine Agonists/urine , Electrodes , Flow Injection Analysis , Humans , Hydrogen-Ion Concentration , Indicators and Reagents , Piribedil/urine , Plasticizers , Potentiometry , Regression Analysis , Solutions , Tablets , Temperature
18.
J Pharm Biomed Anal ; 37(1): 195-8, 2005 Feb 07.
Article in English | MEDLINE | ID: mdl-15664762

ABSTRACT

The electrochemical oxidation of bromocriptine at glassy carbon electrode has been carried out in Britton-Robinson (B-R) buffer solutions in the pH range 2.0-11.0 employing cyclic, linear sweep and differential pulse voltammetry (DPV). Bromocriptine showed one well-defined oxidation peak accompanied by a smaller one. The oxidation process was found irreversible. For analytical purposes, the well-resolved diffusion controlled voltammetric peak at pH 5 was critically investigated. The linear relationship between peak current height and bromocriptine concentration allowed the differential pulse voltammetric determination of the drug over a wide concentration range, from 0.04 to 5.00 microg ml(-1) with a detection limit of 0.01 microg ml(-1). A relative standard deviation of 1.44% at 0.1 microg ml(-1) level was obtained. The proposed DPV method was successfully applied for the individual tablet assay to verify the uniformity content of bromocriptine in commercial tablets.


Subject(s)
Bromocriptine/analysis , Dopamine Agonists/analysis , Carbon , Electrochemistry , Electrodes , Glass
19.
Se Pu ; 23(6): 633-5, 2005 Nov.
Article in Chinese | MEDLINE | ID: mdl-16498994

ABSTRACT

A high performance liquid chromatography-mass spectrometry (LC-MS) analytical method for illicit drugs, apomorphine, sildenafil and alprostadil, in medicines for erectile dysfunction has been developed. The samples were extracted with methanol using ultrasound-assisted extraction. The chromatographic separation was performed on a Zorbax Eclipse XDB-C18 column using acetonitrile-0.5% formic acid aqueous solution as mobile phase. The three compounds were identified by retention time and m/z and quantified by peak area. The results demonstrated that the linear ranges were 50.0 - 5 000.0 microg/L, 10.0 - 1 000.0 microg/L, 40.0 - 4 000.0 microg/L, with detection limits of 20.0, 4.0, 10.0 microg/L for apomorphine, sildenafil and alprostadil, respectively. The average recoveries and the relative standard deviations were 89% - 95% and 9.5% - 11%. The method is simple, rapid, accurate and suitable for the simultaneous determination of these drugs in medicines for erectile dysfunction.


Subject(s)
Alprostadil/analysis , Apomorphine/analysis , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/analysis , Erectile Dysfunction/drug therapy , Mass Spectrometry/methods , Piperazines/analysis , Sulfones/analysis , Alprostadil/therapeutic use , Apomorphine/therapeutic use , Dopamine Agonists/analysis , Dopamine Agonists/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Humans , Male , Phosphodiesterase Inhibitors/analysis , Phosphodiesterase Inhibitors/therapeutic use , Piperazines/therapeutic use , Purines/analysis , Purines/therapeutic use , Sildenafil Citrate , Sulfones/therapeutic use
20.
Analyst ; 122(10): 1007-13, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9463947

ABSTRACT

The chromatogram of ropinirole in the presence of about 5% of a closely eluting impurity, obtained by HPLC with diode-array detection, was analysed by chemometric procedures. Log eigenvalue plots were used to determine the relative composition of regions of the chromatogram. It is shown that since the peaks exhibit tailing, unusual behaviour is found in the plots. This is verified by performing simulations, in which it is demonstrated that peak asymmetry has a pronounced influence on this chemometric approach. In many cases of liquid chromatographic analysis, asymmetric peak shapes are encountered and methods for peak purity assessment should be re-evaluated in the light of these asymmetries.


Subject(s)
Dopamine Agonists/analysis , Drug Contamination , Indoles/analysis , Chromatography, High Pressure Liquid/methods , Statistics as Topic
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