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| Paper Type | : | Research Paper |
| Title | : | Development and validation of simple and rapid LC-MS/MS method for ezetimibe in human plasma and its application to bioequivalence study |
| Country | : | Korea. |
| Authors | : | Yong Sun Park || Dong Pil Kim || Suk Hong Kang || Ki Tak Kim || Yong Hwan Kim || Jong Hoon Kim || Ye Na Kim || Jin Young Kim || Soo Ji Sim || Bo Ra Jin || Heon Soo Lee |
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: | 10.9790/3008-1204070108  |
Abstract: A sensitive and specific liquid chromatography combined with electrospray ionization (ESI) tandem mass spectrometry (LC-MS/MS) method, operating in the negativeionization mode, for quantifying of ezetimibe in human plasma using ezetimibe-d4 as internal standard (IS) was developed and validated. The analyte and IS were extracted by simple one step liquid to liquid extraction (LLE). The chromatographic separation was performed on a Gemini C18 column (50 X 2.0 mm, 5 um) under isocratic conditions using a mixture of acetonitrile/0.1% formic acid (70:30, v/v) as mobile phase at a flow rate of 0.20 ml/min. Quantitation was performed using multiple reaction monitoring (MRM) mode.......
Keywords: Ezetimibe, Human plasma, LC–MS/MS, Pharmacokinetics
[1] Altmann S.W., Davis H.R. Jr, Zhu L.J. et. al. Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption
[2] Davis H.R. Jr, Tershakovec A.M., Tomassinin J.E. et. al. Intestinal sterol transporters and cholesterol absorption inhibition. Curr Opin Lipidol, 22, 467-478, 2011
[3] M.H. Davidson, J. Voogt, J. Luchoomun et. al. Inhibition of intestinal cholesterol absorption with ezetimibe increases components of reverse cholesterol transport in human. Atherosclerosis, 230(2), 322-329, 2013
[4] Sudhop T., Lütjohann D., Kodal A. et. al. Inhibition of intestinal cholesterol absorption by ezetimibe in humans. Circulation, 106(15), 1943-1948, 2002Wang J., Wang J. L., Bao H., RP-HPLC determination of ezetimibe. Chin. J. New Drugs, 12, 932-937, 2003
[5] Sudhop T., Reber M., Tribble D. et. al. Changes in cholesterol absorption and cholesterol synthesis caused by ezetimibe and/or simvastatin in men. J. Lipid Res, 50, 2117-2123, 2009
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| Paper Type | : | Research Paper |
| Title | : | Status of Oxidant and Antioxidant in Patients with Gynaecological Malignancy Undergoing Therapy |
| Country | : | India. |
| Authors | : | Suman Gautam || Seema Mehrotra || M.L.B Bhatt || komal S Pasi || B Anjum || A.A Mahdi |
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: | 10.9790/3008-1204070913 |
Abstract: The present study was undertaken in patients of gynaecological malignancy including carcinoma cervix, endometrium and ovarian to evaluate the status of oxidative stress and antioxidant defence mechanisms after radiotherapy, surgery and chemotherapy. Circulating plasma lipid peroxides as malondialdehyde [MDA] and activities of the defensive enzymes Superoxide Dismutase [SOD] and Catalase [CAT] were measured. Blood samples were collected before treatment and withinally 55 patients in Obstetrics and Gynaecology ward with pre-eclampsia who satisfy the inclusion and exclusion criteria were enrolled...........
Keywords: chemotherapy, radiotherapy, cervical, ovarian, cancer
[1] Ray G, Husain SA. Oxidants, antioxidant and carcinogenesis. Ind J Exp Biol. 2002; 40:1213-32.
[2] Singh R, Singh R.K, Mahdi AA, Misra S, Rai SP, Singh D, et al . Studies on circadian periodicity of urinary corticoids in carcinoma of the breast. In Vivo 1998; 12:69-73.
[3] Singh R, Singh RK, Mahdi AA, Singh RK, Kumar A, Tripathi AK. Circadian periodicity of plasma lipid peroxides and other anti-oxidants as putative markers in gynecological malignancies. In Vivo 2003; 17:593-600.
[4] Miccadei S, Di Venere D, Cardinali A, Romano F, Durazzo A, Foddai MS.Antioxidative and apoptotic properties of polyphenolic extracts from edible part of artichoke (Cynara scolymus L)on cultured rat hepatocytes and on human hepatoma cells. Nutr Cancer 2008; 60: 276-283.
[5] Weijl NI, Cleton FJ, Osanto S. Free radicals and antioxidantsin chemotherapy-induced toxicity.Cancer Treat Rev 1997; 23:209-40..
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| Paper Type | : | Research Paper |
| Title | : | Seasonal variation of heavy metals in selected stations of Periyar river at Ernakulam district, Kerala, India |
| Country | : | India |
| Authors | : | Asha Raj Kariyil Rajappan || Mundanchery Lonan Joseph |
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: | 10.9790/3008-1204071424 |
Abstract: Pollution status of heavy metals like nickel, zinc, arsenic and cadmium in water, sediment and the corresponding bioaccumulation in biomass of Anabas testudineus from different stations of periyar river at ernakulam district during three seasons of an year was analysed. Result showed that the concentration of heavy metals was higher in the water, sediment, biomass from station I and II than control station indicating the pollution status of the river system. The metal bioaccumulations in tissues may be related to the influx of metals from the industries on the banks of the River and their increased........
Keywords: heavy metal, periyar, Anabas testudineus
[1] T.E. Abdel-Baky,et al. Environmental impact assessment of pollution in Lake Manzala, I-Distribution of some heavy metals in water and sediment. J. of Egyp. Ger. Soc. for Zoo., 26 (B), 1998, 25–38.
[2] O.J. Aderinola,et al. Heavy Metals in Surface Water, Sediments, Fish and Perwinkles of Lagos Lagoon American-Eurasian. Journal Of Agricultural & Environmental Sciences, 5(5), 2012, 609–617.
[3] M. Ali and A. Abdel-Satar, Studies of some heavy metals in water, sediment, fish and fish diets in some fish farms in El-Fayoum province. Egyptian Journal of Aquatic Research, 31(2), 2005, 261–273.
[4] American Public Health Association (APHA), Standard Methods for Estimation of Water and Wastewater, 19th ed., American Water Works Association, Water environment Federation, Washington, 1995.
[5] F. Andersen, et al. Interaction between two dietary levels of iron and two forms of ascorbic acid and the effect on growth, anti oxidant status and some non-specific immune parameters in Atlantic salmon (Salmo salar) smolts. Aquaculture,161, 1998, 437–451...
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| Paper Type | : | Research Paper |
| Title | : | Phytochemical Screening of some Wild Plants from Wadi Yalmlam, Saudi Arabia |
| Country | : | India |
| Authors | : | Amal Y. Aldhebiani || Mufarah N |
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: | 10.9790/3008-1204072527 |
Abstract: Wadi Yalmlam is one of the important Wadies in Saudi Arabia with annual rainfall of 200 millimeter. Plants are mainly contained water and many essential organic nutrients. Twenty plant species belonging to fifteen families from Wadi Yalmlam in Saudi Arabia were investigated for their phytochemical constituents. Flavonoids, tannins, saponinns and resin were detected in different plants following different protocols. Tannins was found in 15 species and was the most common distributed compound in most plants. Flaovonoids and saponins were detected in 13 different taxa. Finally, Resin was present in three species only. In conclusion, plants contained many different substances that can be used in medicine to treat many human and plant diseases.
Keywords: Saudi Arabia, Wadi Yalmlam, flavonoids, tannins, saponins, resin, phytochemical constituents.
[1] Aly M.M. and Bafiel S. (2008). Screening for antimicrobial activity of some medicinal plants in Saudi Arabia. World conference on medical and aromatic, 2008. [2] Aly M.M. and Bafeel S. (2010). Screening for antifungal activities of some medicinal plants used traditionally in Saudi Arabia. J Appli Anim Res., 38:39–44. [3] Anderson R. C., Vodovnik M., Min B. R., Pinchak W. E., Krueger N. A., Harvey R. B., et al. (2012). Bactericidal effect of hydrolysable and condensed tannin extracts on Campylobacter jejuni in vitro. Folia Microbiol., 57253–25810
[4] Augustin J.M., Kuzina V., Andersen S.B, Bak S. (2011). Molecular activities, biosynthesis and evolution of triterpenoid saponins. Phytochemical, 72(6):435-57.
[5] Dawid C. and Hofmann T. (2012). Identification of sensory-active phytochemicals in Asparagus (Aspragaus officinalis L.). J Agric Food Chem. 60(48):11877-88..
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| Paper Type | : | Research Paper |
| Title | : | Determination of Shape and Angle of Blood Drop Pattern In Relation To Height on Different Surfaces |
| Country | : | India |
| Authors | : | Geetam Shukla || A.k. Gupta || Vaibhav Saran |
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: | 10.9790/3008-1204072833 |
Abstract: Blood drops and blood drop pattern are some of the most common form of physical evidence encountered during the forensic investigation of incidents involving violence against a person. This study was carried out at Sam Higginbottom University of Agriculture, Technology and Sciences, Allahabad. The purpose of the study to determine the angle and shape of blood drop pattern analysis on soil, coaltaar, and footpath (cemented block) surfaces were considered. Scientific stand, dropper, measuring scale, pin, thread, protector and discarded blood were used for the purpose of observation...........
Keywords: Blood drop pattern soil, Coaltaar, footpath, angle of impact, shape, approximately
[1] Adam, Craig D. (2013); "Experimental and theoretical studies of the spreading of bloodstain on painted surface." Forensic Science International, Volume 229, Issues 1–3, 10 June 2013, Pages 66-74.
[2] Andonoff, Addison, Carbery, Emily and Kriss Brianna (2011); "The effect of angle of wood on simulated blood spatters." Forensic Science Research Abstract. (4),
[3] Balthazard, V., Piedelievre, R., Desoille, H. and DeRobert, L. Etude des Gouttes, de Sang Projects (1939) (Study of Projected Drops of Blood). Ann Med Leg Criminal Police Sci Toxicol. 1939; 19: 265-323.
[4] Bevel, T. and Gardner, R. M. (2002) Bloodstain Pattern Analysis: With an introduction to Crime Scene Reconstruction, 2nd Ed. Boca Raton, FL: CRC Press,37.
[5] Boonkhong Kittipat, Karyanadech Montri and Aiyarak Pattara, (2010); "Impact angle analysis of bloodstains using a simple image processing technique" Songklanakarrin, J. Sci. Technol 32(2), 169-173
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| Paper Type | : | Research Paper |
| Title | : | Therapeutic activities ofArtemesiaherba-alba and Rosmarinus officinalis against microbial infection: A review |
| Country | : | Malaysia |
| Authors | : | Abdinasir Yusuf Osman || Fathy Mohamed Ali || Muhammad Luqman Nordin || Mohd Mokhtar Arshad || Rumaizi Shaari || Zainal Abidin Abu-Hassan || Nazlina Ibrahim |
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: | 10.9790/3008-1204073438 |
Abstract: Natural products are still major potential sources of innovative therapeutic agents for various conditions, including infectious diseases as they represent an unmet source of chemical diversity. This study was conducted to determine the anti-trypanosomal properties of Artemisia herba-alba and Rosmarinus officinalis in vivo settings. We have reviewed previous studies in the literature, which support the therapeutic activity of these plants and the data suggest that A. herba-alba as well as R. officinalis have anti-trypanosomal activites, and reinforce the use of this plant as an alternative remedy for microbial infection in traditional medicine.
Keywords: Artemsia herba-alba, Rosmarinus officinalis, anti-trypanosomal properties
[1] Akrout, A., Mighri, H., Krid, M., Thabet, F., Turki, H., El-Jani, H., &Neffati, M. (2012). Chemical composition and antioxidant activity of aqueous extracts of some wild medicinal plants in Southern Tunisia. International Journal of Life Science and Medical Science, 2(1), 1-4.
[2] Al-Shamaony, L., Al-Khazraji, S. M., &Twaij, H. A. (1994). Hypoglycaemic effect of Artemisia herbaalba. II. Effect of a valuable extract on some blood parameters in diabetic animals. Journal of Ethnopharmacology, 43(3), 167-171.
[3] Altinier G, Sosa S, Aquino RP, Mencherini T, Loggia RD, Tubaro A (2007). Characterization topical anti-inflammatory compounds in Rosmarinus officinalis L. J. Agri. F. Chem., 55: 1718-23.
[4] Awad, F. M. A., Mohamed, M. A., Osman, A. Y., Abu-Hassan, Z. A., & Ibrahim, N. (2014). In vivo assessment of anti-trypanasomal effect of rosemary (Rosmarinus officinalis) in rabbits. IOSR J Agric Vet Sci, 7, 45-54.
[5] Awad, F. M., Hasan, Z. A. B. A., & Osman, A. Y. (2013). Antitrypanosomal effects of crude ethanolic extract of Artemisia herbaalbafollwing experimental infection of rabbits.
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| Paper Type | : | Research Paper |
| Title | : | Cytotoxic effect ofCladophoraglomeratacrude extracts andphytolin bone marrow of mice |
| Country | : | Iraq |
| Authors | : | Lamiaa A. Gharb |
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: | 10.9790/3008-1204073943 |
Abstract: Cladophoraglomerata contain different active compounds like flavonoids, alkaloids, phenols and tannins, fatty acids, sterols, terpeneswhich could be used as a novel source of natural agents for pharmaceutical industries. Some Studies that determined the activity of immune system and the effects of different agents depended on the cells division in bone marrow as it is the source of all blood cells. Two different doses (50,150 mg/ kg) from algal crude extracts and phytol were used in this study to determine the activity of these extracts on Mitotic index and Blast index in mice bone marrow.............
Keywords: Algae, Cladophoraglomerata, ethanolic extract, mitotic index, phytol
[1] E. Ramin. Comparison of East African and Iran natural feeding condition based on the chemical and biochemical properties of lake algae .African Journal of Environmental Science and Technology, 7(9),2013,857-861.
[2] S. N.Higgins,S. Y.Malkin,E. T.Howel, S. J. Ildford,L.Campbell ,V. H. Baer and R.E. Hecky, An ecological review of Cladophoraglomerata (Chlorophyta) in the laurentian great lakes. Journal of Phycology, 44(4), 2008, 839 – 854.
[3] D.Y.Mohamed, A.S.Dwaish, G. A. Ali and A. L. M.Jawad.Use of CladophoraglomerataExtract against Multidrug Resistant Bacterial Pathogens.Journal of Environmental Science and Engineering,2013, 495-500.
[4] R.Laungsuwonand W. Chulalaksananukul. Chemical composition and antibacterial activity of extracts from freshwater green algae, CladophoraglomerataKützing and Microsporafloccosa(Vaucher) Thuret.Journal of BioScience and Biotechnology. 3(3),2014, 211-218.
[5] M.N.Khalid, M. Shameel and V.U. Ahmad.The Bioactivity and Phycochemistry of Two Species of Cladophora(Siphonocladophyceae) from Sindh.Pakistan Academy of Sciences.49 (2),2012, 113-121.
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| Paper Type | : | Research Paper |
| Title | : | In-silico analysis of active compounds has potential inhibitors against diabetic |
| Country | : | India |
| Authors | : | Palanisamy Prakash || Rengarajan Manivasagaperumal |
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: | 10.9790/3008-1204074449 |
Abstract: Plants are naturally produced important sources of medicines. Today, a large number of drugs in use derived from plants. A Decalepis hamiltonii (Asclepiadaceae) to treat the various diseases of to human such as diabetic and cancer. GC MS Analysis was carried out to identify the compounds of the selected drug and In silico studies carried out to assess the antidiabetic potential. In silico docking exercise of different herbal based ligands with anti-diabetic properties, revealed that PBRƴ got docked onto diabetic protein with the lowest calculated interaction energy............
Keywords: Methanol, root, Decalepis hamiltonii, anti-diabetic protein
[1] Kumar and V. Navaratnam, Neem (Azadirachta indica): Prehistory to contemporary medicinal uses to humankind. Asian Pac. J. Trop. Biomed.,2013 3(7): 505 - 514.
[2] Nayar, R.C., J.K.P. Shetty, Z. Mary and Yoganarshimhan,. Pharmacognostical studies on the root of Decalepis hamiltonii Wight and Arn and comparison with Hemidesmus indicus (L) R.Br; 1978.,5(6).
[3] Kim, S.J., A.R. Cho and J. Han,. Antioxidant and antimicrobial activities of leafy green vegetable extracts and their applications to meat product preservation. Food Control., 2013., 29: 112–120.
[4] Piccagli,L., E. Fabbri, M. Borgatti, V. Bezzerri, I. Mancini, E. Nicolis, M.C. Dechecchi, I. Lampronti, G. Cabrini and R. Gambari. Docking of molecules identified in bioactive medicinal plants extracts into the p50 NF-kappaB transcription factor: correlation with inhibition of NF-kappaB/DNA interactions and inhibitory effects on IL-8 gene expression BMC Structural Biol., 2008.,8:38
[5] RajaNaikaa, H., V. Krishnab, K. Lingarajua, V. Chandramohanc, M. Dammallic, P.N. Navyac and D. Sureshda 2. Molecular docking and dynamic studies of bioactive compounds from Naravelia zeylanica (L.) DC against glycogen synthasekinase-3protein. J. Taibah Uni. for Sci., 015., 9: 41–49.
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| Paper Type | : | Research Paper |
| Title | : | Analysis of Post Blast Residue Material in Soil Sample for Forensic Consideration |
| Country | : | India |
| Authors | : | M.K. Mishra || Gaurav Kumar Jaiswal |
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: | 10.9790/3008-1204075052 |
Abstract: The terrorist activities in recent years have urged the need for rapid and accurate forensic investigation on post-blast evidences. The analysis of explosives and their degradation products in soils are important to enable forensic scientist to identify the explosives used in the explosion and establish possible links to their likely origin. Anions of interest for post-blast identification of low explosives were chemically analyzed. The explosives comprised of the blast residue materials of various samples which are found at suspected crime scene. In residue materials, (ClO3-, K+, Al3+, B2+,S2- )were identified. However, inorganic substance of anion was found present in post-blast soil samples. The anions analysis was indicative that residue materials were being used as post blast soil sample ingredients. It is important to know that the post blast evidences either low or high explosive.
Keywords: Anions, homemade low explosives, black powder, post-blast soil samples
[1] Ahmad, U.K. and Kiu, K.H. (2007). Solid Phase Microextraction-Gas Chromatography for the Analysis of Explosives in Post Blast Water Samples, Jurnal Teknologi, 46(C), 59-74.
[2] Ahmad, U.K., Rajendran, S, Lee. L.W. and Yew, C.H. (2008). Forensic Analysis of High Explosives Residues in Post-Blast Water Samples Employing Solid Phase Extraction for Analyte Preconcentration. Malays. J. Anal. Sci. 12(2): 367-374.
[3] Ahmad, U.K., Lee, W.L. and Yew, C.H. (2011). Direct Immersion Solid Phase Microextraction for the Forensic Determination of Nitro Explosives in Post-Blast Water Samples. Health Environ. J. 2 (1):27-37.
[4] Burmeister, S. G. McCord, B. R., Hargadon, K. A., Hall, K. E. (1994). Forensic Analysis of Explosives Using Ion Chromatographic Methods. Anal. Chem. Acta 288: 43-56.
[5] Beveridge A. (1998). Forensic Investigation of Explosions. London: Taylor & Francis Ltd
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| Paper Type | : | Research Paper |
| Title | : | Identification and Sequences of Two LeishmaniaSpecies Isolated From Human Cutaneous Lesion in Iraq |
| Country | : | Iraq |
| Authors | : | AbdulKareemAakoolAl-Tamemy || Noor Naeem Shakir Al-Qurashi |
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: | 10.9790/3008-1204075357 |
Abstract: Total 80 specimens collected passively from patients with cutaneous ulcers suggestive of leishmaniasis attending hospital and health centers in all parts of Iraq for diagnosis were included in the study. Microscopic examination of dermal Giemsa-stained smears scrapings revealed LD bodies in 60 (75%)samples gave positive results whereas Nested PCR detectLeishmaniaparasite in 68(85% ) samples;the cutaneousleishmaniasis (CL) in Iraq are caused by two species of Leishmania.There are only seven positive cases was detected as L. Tropicathat distribute in city center and sixty one is L............
Keywords: Cutaneous leishmaniasis, Sequence.Phylogenetic tree. Nested PCR.
[1] de Vries, H. J., Reedijk, S. H., &Schallig, H. D. (2015). Cutaneous leishmaniasis: recent developments in diagnosis and management. American journal of clinical dermatology, 16(2), 99.
[2] World Health Organization. Control of the leishmaniasis. Report of a meeting of the WHO Expert Committee on the Control of Leishmaniasis, 2010, Geneva, 22-26 March 2010. WHO technical report series 949. Geneva: World Health Organization; 2010
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| Paper Type | : | Research Paper |
| Title | : | A Novel Stability Indicating Reverse Phase Ultra Performance Liquid Chromatography Method Development and Validation for Estimation of Related Compounds of Parecoxib Sodium in Parecoxib Sodium for Injection |
| Country | : | India |
| Authors | : | Dhananjay P. Dwivedi || B. Ravi Kumar || Sridhar.Y || Prof.J. Sreeramlu |
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: | 10.9790/3008-1204075867 |
Abstract:A new and rapid stability-indicatingreversed-phase ultra performance liquid chromatography (UPLC) method was developed and validated for determination of Parecoxibimpurities in Injectionformulation. The chromatographic separation was carried out on an Acquity UPLC BEH C18, (100mmx2.1mm) 1.7μmusing a mobile phase consisting of Potassium dihydrogen phosphate buffer with pH 6.5, acetonitrile and methanol using gradient programme at a flow rate of 0.30 ml/min with an injection volume of 2μL andthe UV detection was performed at 240 nm. The method was validated for precision, accuracy, specificity, linearity, sensitivity and robustness. The proposed method can be applied for quality control, release and stability analysis of Parecoxib impurities in Injection formulation.
Keywords: Parecoxib, Stability-indicating, UPLC, Validation.
[1] Fanali, S., Haddad, P., Poole, C., Schoenmakers, P., & Lloyd, D.(2013). Liquid chromatography. Waltham, MA: Elsevier.
[2] International Conference on Harmonization (ICH) of Technical Requirements for the Registration of Pharmaceutical for Human Use, Validation of Analytical Procedures: Methodology (ICH-Q2B). November 1996;1-8.
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[4] Bakshi M, Singh S, Development of validated stability indicating assay methods critical review. J Pharm Biomed. 2002:28:1011-1040.
[5] Saccomanni G1, Giorgi M, Del Carlo S, Manera C, Saba A, Macchia M.Simultaneous detection and quantification of parecoxib and valdecoxib in canine plasma by HPLC with spectrofluorimetric detection: development and validation of a new methodology.AnalBioanal Chem. 2011 Sep;401(5):1677-84. doi: 10.1007/s00216-011-5244-4. Epub 2011 Jul 19.
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| Paper Type | : | Research Paper |
| Title | : | GC and GC-MS analysis of the dried Leaf and Rhizome essential oil of Curcuma aurantiaca Zijp. (Zingiberaceae) |
| Country | : | India |
| Authors | : | Rajesh Kumar T || SanthoshKumar R || Yusuf Akkara |
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: | 10.9790/3008-1204076875 |
Abstract: The chemical investigation on volatile oil obtained by hydrodistillation of air dried leaves and rhizome of Curcuma aurantiaca Zijp. (Zingiberaceae) from Southern india done by GC and GC-MS. The major constituents of the above oils were Caryophyllene (31.07%), 7,11-dimethyl- 3-methylene-(E)- (17.30%), Camphene(4.25%),Beta.-Pinene (2.18% ), Phytol (11.32%), Benzofuran (9.06%), alpha-Caryophyllene(3.49%), n-Hexadecanoic acid (2.69%), Naphthalene(2.12%), Caryophyllene oxide (1.83%).This is the first report on the chemical compounds of the essential oil of this species.
Keywords: Curcuma aurantiaca Zijp; Rainbow ginger; Zingiberaceae; Essential oil composition; GC-MS; Caryophyllene; Beta-Pinene; Naphthalene; Camphene.
[1] Adams R P 1989. Identification of essential oil components by gas chromatography/mass spectrometry.Allured Publ. Corp., Carol Stream 1995.
[2] AOAC 1975. Official methods of analysis 12th ed. Association of official Analytical Chemists, Washington, DC P. 1094.
[3] Burt S 2004. Essential oils: their antibacterial properties and potential applications in foods-a review. Int. J. Food Microbiol. 94, 223-253.
[4] Clevenger J F 1928. Apparatus for the determination of volatile oil.J. Am. Pharm. Assoc. 13: 346.
[5] Gildemeister E and Hoffmann Fr. 1956. Die Aetherischen Oele, 4th ed. Vol 4. Akademic Verlag, Berlin, P. 489.