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- Quantitative thin-layer chromatographic method for determination of amantadine hydrochloride. [Journal Article]
- Int J Biomed Sci 2008 Jun; 4(2):155-60.
A simple and accurate thin-layer chromatographic (TLC) method for quantitative determination of amantadine hydrochloride (AMD) was developed and validated. The method employed TLC aluminum plates pre-coated with silica gel 60F-254 as a stationary phase. The solvent system used for development consisted of n-hexane-methanol-diethylamine (80: 40: 5, v/v/v). The separated spots were visualized as brown spots after spraying with modified Dragendorff's reagent solution. Amantadine hydrochloride was subjected to accelerated stress conditions: boiling, acid and alkaline hydrolysis, oxidation, and irradiation with ultraviolet light. The drug was found to be stable under all the investigated stress conditions. The method was validated for linearity, limits of detection (LOD) and quantitation (LOQ), precision, robustness, selectivity and accuracy. The optical densities of the separated spots were found to be linear with the amount of AMD in the range of 5-40 µg/spot with good correlation coefficient (r=0.9994). The LOD and LOQ values were 0.72 and 2.38 µg/spot, respectively. Statistical analysis proved that the method is repeatable and accurate for the determination of AMD. The method, in terms of its sensitivity, accuracy, precision, and robustness met the International Conference of Harmonization/Federal Drug Administration regulatory requirements. The proposed TLC method was successfully applied for the determination of AMD in bulk and capsules with good accuracy and precision; the label claim percentages were 99.0 ± 1.0%. The results obtained by the proposed TLC method were comparable with those obtained by the official method. The proposed method is more advantageous than the previously published chromatographic methods as it involved the most simple chromatographic technique; TLC. In addition, method relies on the use of inexpensive equipment, a scanner and software, and not critical derivatizing reagent, thus maximizing the ability of laboratories worldwide to analyze samples of AMD.
- Determination of rimantadine in human urine by HPLC using a monolithic stationary phase and on-line post-column derivatization. [JOURNAL ARTICLE]
- J Sep Sci 2013 Mar 21.
In the present study, we propose the first HPLC method coupled to postcolumn derivatization for the determination of rimantadine in human urine samples. The analyte and amantadine (internal standard) were isocratically separated using an RP monolithic stationary phase (100 × 4.6 mm id) with a mobile phase consisting of CH3 OH/phosphate buffer (25 mmol/L, pH 3.0) at a volume ratio of 50:50. Postcolumn derivatization involved on-line reaction with o-phthalaldehyde (20 mmol/L) and N-acetyl-cysteine (5 mmol/L) at alkaline medium (100 mmol/L borate pH 11.0). Spectrofluorimetric detection at λex /λem = 340/455 nm enabled the selective and sensitive determination of rimantadine in urine samples at a range of 50-500 ng/mL with an LOD of 5 ng/mL. Human urine samples were analyzed successfully after SPE using hydrophilic-lipophilic balanced RP cartridges (30 mg/mL, Oasis HLB). Recoveries ranged between 89.7 and 102.7%.
- Genetic diversity of early (1998) and recent (2010) avian influenza H9N2 virus strains isolated from poultry in Iran. [JOURNAL ARTICLE]
- Arch Virol 2013 May 3.
Infection with avian influenza H9N2 virus is widespread in the Asian poultry industry, resulting in great economic losses due to mortality and a severe decline in egg production. To obtain more-comprehensive genomic data from circulating H9N2 viruses in Iran, we sequenced the whole genomes of early (Ck/IR/ZMT-101/98) and recent (Ck/IR/EBGV-88/10) isolates of this virus in Iran. The M and NS genes of Ck/IR/EBGV-88/10 shared a high level of similarity with a highly pathogenic H7N3 virus isolated from Pakistan. The cleavage site within the HA protein of these viruses contained two different motifs, RSSR and KSSR, which are similar to those found in low-pathogenic viruses. The deduced amino acid sequence of the new isolate contained the mutation Q226L, which is a characteristic of human-type sialic acid influenza receptor binding. An analysis of the viral amino acid sequence of the M2 protein of the recent strain revealed a V27A mutation, which is associated with amantadine resistance in avian influenza virus. The present results emphasize the need for continuous surveillance of H9N2 viruses in poultry and the human population to obtain more information about the nature and evolution of future pandemic influenza viruses.
- Diagnosis and treatment of impulse control disorders in patients with movement disorders. [Journal Article]
- Ther Adv Neurol Disord 2013 May; 6(3):175-88.
Impulse control disorders are a psychiatric condition characterized by the failure to resist an impulsive act or behavior that may be harmful to self or others. In movement disorders, impulse control disorders are associated with dopaminergic treatment, notably dopamine agonists (DAs). Impulse control disorders have been studied extensively in Parkinson's disease, but are also recognized in restless leg syndrome and atypical Parkinsonian syndromes. Epidemiological studies suggest younger age, male sex, greater novelty seeking, impulsivity, depression and premorbid impulse control disorders as the most consistent risk factors. Such patients may warrant special monitoring after starting treatment with a DA. Various individual screening tools are available for people without Parkinson's disease. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease has been developed specifically for Parkinson's disease. The best treatment for impulse control disorders is prevention. However, after the development of impulse control disorders, the mainstay intervention is to reduce or discontinue the offending anti-Parkinsonian medication. In refractory cases, other pharmacological interventions are available, including neuroleptics, antiepileptics, amantadine, antiandrogens, lithium and opioid antagonists. Unfortunately, their use is only supported by case reports, small case series or open-label clinical studies. Prospective, controlled studies are warranted. Ongoing investigations include naltrexone and nicotine.
- Genomic signature and protein sequence analysis of a novel influenza A (H7N9) virus that causes an outbreak in humans in China. [JOURNAL ARTICLE]
- Microbes Infect 2013 Apr 27.
Very recently, a new avian flu outbreak in humans, which is caused by a novel H7N9 influenza A virus (AIV), was reported in China. As of April 13, 2013, 49 confirmed cases (mainly middle-aged to elderly males), including 11 deaths, were reported in China. Here we analyzed the genomic signatures and protein sequences of the human H7N9 AIVs. We found that the genomic signatures of A(H7N9) had high and low identity to avian and human IAVs, respectively, suggesting its avian origin. The signature amino acids of A(H7N9) had high identity to 1997 H5N1 and 2009 H1N1, but low identity to those influenza strains that caused pandemics before 1980. One of the key signature amino acids at 627 in PB2 mutated to lysine, which is associated with mammalian adaptation and increased virulence of the highly pathogenic avian influenza A(H5N1) virus. Besides, several other human-like signatures, including PB2-44S, PA-100A, PA-356R, and PA-409N are also found in this avian-origin A(H7N9) virus. The HA protein has the Q226L mutation, which is associated with increased binding to mammalian-like receptors bearing alpha 2,6 receptor in the human upper airway. The M2 protein contains the N31S mutation, suggesting its resistance to the M2 channel blockers amantadine and rimantadine. These findings suggest that this avian-origin AIV gains its bird-to-human, i.e., zoonotic, transmissibility and increased virulence, as well as drug-resistance, by mutating key signature amino acid residues and those in the functional domains of the viral proteins. Therefore, it is prudent to monitor the evolution of A(H7N9), as well as develop strategies to combat any potential epidemic or pandemic.
- New Strategy for High Throughput Screening of Anti- Influenza virus M2 Ion Channel Inhibitors. [JOURNAL ARTICLE]
- Curr Pharm Des 2013 Apr 26.
Since the recent emergence of swine and avian flu, there has been a sense of urgency to discover new anti-influenza drugs. In this study, a stable cell line with M2 ion channel/ enhanced Green fluorescent protein (EGFP) co-expression was established in order to develop an EGFP-based high-throughput assay for screening M2 ion channel inhibitors. This assay directly monitors the proton conductivity of the M2 ion channel by measuring the fluorescence intensity of EGFP, which is dependent on and sensitive to pH. The ability of amantadine to inhibit the M2 ion channel was detected by this novel EGFP-based assay and then confirmed by a patch clamp recording assay. With this assay, (1S,2S,3S,5R)-(+)-3-Isopinocampheylamine and (1R,2R,3R,5S)-(-)-3-Isopinocampheylamine were identified to inhibit M2 ion channel with an antiviral profile similar to that of amantadine. This new technique will facilitate the discovery of pharmaceutical candidates and will aid in the development of new, potent, and safe anti-influenza agents.
- Combined use of electroconvulsive therapy and amantadine in adolescent catatonia precipitated by cyber-bullying. [Journal Article]
- J Child Adolesc Psychopharmacol 2013 Apr; 23(3):228-31.
- [Rapid identification 15 effective components of anti common cold medicine with MRM by LC-MS/MS]. [English Abstract, Journal Article]
- Yao Xue Xue Bao 2013 Jan; 48(1):94-7.
This paper reports the establishment of a method for rapid identification 15 effective components of anti common cold medicine (paracetamol, aminophenazone, pseudoephedrine hydrochloride, methylephedrine hydrochloride, caffeine, amantadine hydrochloride, phenazone, guaifenesin, chlorphenamine maleate, dextromethorphen hydrobromide, diphenhydramine hydrochloride, promethazine hydrochloride, propyphenazone, benorilate and diclofenac sodium) with MRM by LC-MS/MS. The samples were extracted by methanol and were separated from a Altantis T3 column within 15 min with a gradient of acetonitrile-ammonium acetate (containing 0.25% glacial acetic acid), a tandem quadrupole mass spectrometer equipped with electrospray ionization source (ESI) was used in positive ion mode, and multiple reaction monitoring (MRM) was performed for qualitative analysis of these compounds. The minimum detectable quantity were 0.33-2.5 microg x kg(-1) of the 15 compounds. The method is simple, accurate and with good reproducibility for rapid identification many components in the same chromatographic condition, and provides a reference for qualitative analysis illegally added chemicals in anti common cold medicine.
- Structural Comparison of the Wild-Type and Drug-Resistant Mutants of the Influenza A M2 Proton Channel by Molecular Dynamics Simulations. [JOURNAL ARTICLE]
- J Phys Chem B 2013 May 9.
The influenza A M2 channel in the viral envelope is a pH-regulated proton channel that is crucial for viral infection and replication. Amantadine and rimantadine are two M2 inhibitors that have been widely used as anti-influenza drugs. However, due to naturally occurring drug-resistant mutations, their inhibition ability has gradually decreased. These drug-resistant mutations are found at various positions on the transmembrane domain of the M2 protein and could be categorized to three types: mutations close to the drug-binding site located at the pore-facing positions (V27A, A30T, S31N, and G34E); mutations at the interhelical interfaces at the N-terminal half of the channel (L26F); and mutations outside the drug-binding site lying at the interhelical interfaces (L38F, D44A). Investigating the structures and the M2-inhibitor interactions of these mutants would illuminate drug inhibition and drug resistance mechanisms and guide the design of novel anti-influenza drugs targeting these drug-resistant mutants. In this study, we chose four mutations at different positions (V27A, S31N, L26F, L38F) and conducted molecular dynamics simulations on both the apo-form and the drug-bound forms. The protein structures as well as the water structure in the channel pore were analyzed. Stable water clusters facilitating drug binding were found. Both the protein pore radius profiles and the structure of the water clusters were sensitive to the mutations. Based on our simulations, we compared the structures of the mutated proteins and proposed possible mechanisms for drug resistance of these mutations.
- [Multi-residue determination of five antiviral drugs in chicken tissues by liquid chromatography-electrospray ionization tandem mass spectrometry]. [English Abstract, Journal Article]
- Se Pu 2012 Dec; 30(12):1253-9.
A method of liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) for the simultaneous determination of five antiviral drug residues, amantadine, rimantadine, memantine, moroxydine and imiquimod in chicken tissues was developed. The compounds were extracted from the samples with trichloroacetic acid solution and acetonitrile, and then cleaned-up by strong cation exchange (SCX) solid phase extraction cartridges. The analytes were separated on a Xamide column (100 mm x 2.1 mm, 5 microm) and determined qualitatively and quantitatively with tandem mass spectrometry using positive polarity mode under multi-reaction monitoring (MRM) scan type. The limits of detection and the limits of quantification were 0.06 - 0.30 microg/kg and 0.2 - 1.0 microg/kg, respectively. The average recoveries of the five drugs were 72.3% - 94.2% in chicken muscle and 70.8% - 92.7% in chicken livers. The relative standard deviations (RSDs) in chicken muscle and livers were 3.5% -11.3% and 5.3% -12.6%, respectively. The method is selective without interference and suitable for the determination and confirmation of the five antiviral drugs in chicken muscle and livers.