Spectrophotometric Determination Methyldopa and Salbutamol by Oxidative Coupling, Cloud Point and Flow Injection in Pharmaceutical Formulations

Total Page:16

File Type:pdf, Size:1020Kb

Spectrophotometric Determination Methyldopa and Salbutamol by Oxidative Coupling, Cloud Point and Flow Injection in Pharmaceutical Formulations Available online on www.ijddt.com International Journal of Drug Delivery Technology 2019; 9(2); 182-192 doi: 10.25258/ijddt.9.2.11 ISSN: 0975 4415 Research Article Spectrophotometric Determination Methyldopa and Salbutamol by Oxidative Coupling, Cloud Point and Flow Injection in Pharmaceutical Formulations Nisreen Kais Abood1*, Mohammed Jasim M Hassan1, Muneer A AL-Da,amy2 1Department of Chemistry, College of Science, Mustansiriyah university Baghdad, Iraq 2Department of Chemistry, College of Education for pure Science, Karbala University, Kerbala Iraq Received: 21st Jan, 19; Revised: 2nd Apr, 19, Accepted: 14th May, 19; Available Online: 25th Jun, 2019 ABSTRACT Three methods study in this research simple, sensitive, an expensive and rapid Oxidative Coupling reaction, Cloud Point Extraction and Flow Injection spectrophotometric methods for determination Methyldopa and Salbutamol, the first method oxidative coupling reaction between the Methyldopa and thiosemicarbazide in presence of ferric nitrate anhydrous to yield dark green colored product that have absorbance at λ max 460 nm. Salbutamol coupling reaction with 4-nitrophenyl hydrazine in presence the potassium Iodide and sodium hydroxide to product the violet colored has absorbance at λ max 530 nm. Beer’s law is obeyed from (1-50) µg/ mL with sandall’s sensitivity (0.039,0.073), correlation coefficient (0.9998) and molar absorptivity (0.536×104,0.327×104) for Methyldopa and Salbutamol respectively. The secondly method to estimation the trace amount of phenolic drugs that product from the oxidative coupling reaction it is cloud point extraction, cloud point extraction enables the drugs to be precisely estimated under the optimal experimental conditions, the maximum absorption at λ max (470,535) nm respectively. The concentration was range (0.25-6) µg/mL, molar absorptivity 0.510×105,0.483×105 and enrichment factor (9.51,14.72) respectively for Methyldopa and Salbutamol .Flow injection analysis is simple method to determination the phenolic is based on the measurement of absorption signal for product resulting from oxidative coupling reaction , study all experimental parameters chemical and physical to development and stability the colored of product .Total flow injection of 1.5mL/min was pumped and active material was detect at λ max (460,530)nm respectively for Methyldopa and Salbutamol . In this the proposed methods were suxciffuly, applied to the determination Methyldopa and Salbutamol in pharmaceutical preparation. Keywords: Oxidative Coupling, Phenolic Drugs, Flow Injection, Cloud Point Extraction, Spectrophotometric. INTRODUCTION spectrophotometric method12. Oxidative Coupling Methyldopa is (β-3,4-dihydroxy phenyl-α-methyl alanine reaction its reaction between two or more from organic MD), It’s a white to yellow-white powder or almost compounds in presence of oxidant agent and the color colorless, soluble in warm distilled water1,2, Methyldopa product can be determining by different methods such as have various pka value depend on the functional group spectrophotometric, polar graphic and 13,14 that found in the structure such as –NH2, -OH and chromatographic , oxidative coupling are applied COOH3,4 the structure fig.1, several methods to successfully in many fields such as pharmaceutical estimation Methyldopa in pharmaceutical preparation agricultural15. Cloud Point Extraction (CPE) it’s titrimetric method, fluorimetry, kinetic measurement, introduced by watanbe and tanaka in 197816,CPE used to potentiometric and flow injection method5,6. Salbutamol estimation various trace metals and drugs, the having Sulfate (SBS) as (rs)-1-(4-hydroxy3- considerable advantages such as simplicity cheapness, hydroxymethylphenyl)-2-(tert-butyl amino) ethanol fast selectivity ,high enrichment factor and low toxicity to sulfate, the salbutamol also known albuterol7 fig. 2. the environment than other extraction method that used Salbutamol is acted as it cardiovascular and the best organic solvents17,18.Flow injection it’s best bronchodilator in fluencies are smaller than it technique characterized as simple, cheap, fast and bronchodilator action drugs which is a common entity in selectivity to estimate the drugs19,20, Flow injection high performance8. Salbutamol is prevalently used by analysis (FIA) system have many interest such as athletes, anti-doping agent9, Salbutamol in increase sample throughput, low reagent consumption, pharmaceutical used in various way to estimation reduce waste production, and inexpensive equipment21,22. oxidative coupling, diazotization and coupling10, intrastation, nitration, charge transfer11, HPLC, EXPERIMENTAL Electrophoresis, Gas chromatography and Instruments *Author for Correspondence: [email protected] Nisreen et al. / Spectrophotometric Determination Methyldopa… Figure 1: Methyldopa Figure 2: Salbutamol SX Thiosemicarbzade pump Ferric nitrate W R.C FC D Figure 3 Figure 4 Figure 3,4: Scheme of employed flow system, P: peristaltic pump, R.C: reaction coil, S: sample injection, W: waste, FC: flow cell Figure 5: Absorption spectrum of oxidative coupling for methyldopa with the reagent against the reagent blank under optimum conditions. Figure 6: Absorption spectrum of oxidative coupling for Salbutamol with the reagent against the reagent blank under optimum conditions. All spectral and absorbance measurement were carried in 7110 and Electronic Balance Mettle AE 200. The Flow signal beam UV Visible spectrophotometer 160. injection configuration A three channel manifold Fig.3 Equipped with 1cm and 0.5 cm quarts’ cell. An for Methyldopa and Fig.4 for Salbutamol was employed Ultrasonic and thermostatic water bath from Elma Hans for (FIA). Peristaltic pump (ALITEA, C4, made in Schmidbauer Gmbh and Co.KG used coupled with Sweden) with polyvinyl chloride tube (0.8) mm internal Extraction of samples. A centrifuge (Shanghai surgical diameter was used for the peristaltic pump and Reaction instrument factory,80-2, Shanghai, Germany) that use to Coil complete the separation of CPE, PH meter, type inoLap Reagents IJDDT, April 2019 – June 2019, Volume 9, Issue 2 Page 183 Nisreen et al. / Spectrophotometric Determination Methyldopa… Table 1: Effect order addition. No. order Order addition of Absorbance of Order addition of Absorbance of Methyldopa Methyldopa salbutamol Salbutamol 1 O+R+D 0.067 R+O+D+B 0.089 2 O+D+R 0.084 R+O+B+D 0.090 3 R+D+O 0.133 R+D+O+B 0.512 4 D+R+O 0.879 D+R+O+B 0.322 5 R+O+D 0.341 D+O+R+B 0.311 D=Drug, R=Reagent, O=Oxidant, B=Base Table 2: Characteristic parameter for the regression The best method was developed to prepared oxidative equation of the proposed oxidative coupling method coupling reaction of Methyldopa by adding 1mL ,1000 for methyldopa and salbutamol. μg/mL Methyldopa,1mL ,1000 μg/mL thiosemicarbazide Parameter Methyldopa Salbutamol and 1mL (0.1) M Fe(NO3)3.9H2O, that gave the dark λ max(nm) 460 530 green colored at λ max (460) nm. Salbutamol (1ml,1000 color Green Violet μg/mL coupling with 1 mL ,0.2 M 4-nitrophenyl linearity range μg/mL 1-50 1-50 hydrazine, 1 mL, 0.1 M KIO3 in presence 0.5ml ,1M 4 4 Molar absorptivity 0.536×10 0.327×10 NaOH that gave violet colored at λ max (530) nm, finally (L.mol-1.cm-1) placed in 20 mL flask complete with distilled water. The Sandell’s sensitivity 0.039 0.073 oxidative coupling formed absorbance dark green, violet 2 (μg/cm ) colored at λ max (460.530) nm for Methyldopa and Correlation coefficient 0.9998 0.9998 Salbutamol respectively. ® General Procedure of Cloud Point Extraction for Regression equation Y=0.0254x Y=0.0137x- Phenolic Drugs - 0.0223 0.0065 The various concentration (0.25-6) μg/mL from the dye of Slope(b) 0.0254 0.0137 oxidative coupling reaction result transfer 1mL from this Intercept(a) -0.0223 -0.0065 product into 15mL of centrifuge tubes ,10% v/v Triton X- Analytical sensitivity 0.065 0.064 114 1 mL add, 2 mL of 0.01 M of surfactant (CTBA) , 2 -1 (μg.ml ) mL from 5% Na2SO4 respectively, after that complete the Limit of detection 0.118 0.218 volume 12.5 mL with distilled water. Test tube put into (μg/mL) ultrasonic thermostatic water bath let it 2 mint to mix the Limit quantification 0.389 0.729 mixture and water bath 40,50ºC for 50 min. Formation μg/mL Cloudy and it is separation into two phase after that C.L. for the 0.0254±0.0 0.0137±0.00 transfer to centrifuge to complete separation two-layer slope(b±tsb)at 95% 00968 05472 organic phase and aqueous phase, decant the aqueous and C.L. for the - - add 0.5 mL ethanol to organic phase to dissolve the dye. intercept(a±tsa) at 95% 0.0223±0.0 0.0065±0.01 1cm cell was used to determination the dye, prepared the 1984 124 blank under in the same way. Standard error for 0.005612 0.00318 General Procedure of Flow Injection regression line (S y/x) A Methyldopa and Salbutamol solution was prepared by different concentration 1-150 μg/mL from the standard All Chemicals were analytical grade. stock solutions working solution 1000 μg/mL. A 100µL portion (1000 μg/mL) Methyldopa and Salbutamol were prepared Methyldopa was injected into stream of 0.2 M by dissolving 0.1 gm of Methyldopa and Salbutamol in thiosemicarbazide the mixture reacted with stream -2 distilled water and dilution to the mark in 100mL (1.5×10 ) M Fe(NO3)3.9H2O, the reaction is carryout via volumetric flask. Stock solution of thiosemicarbzide mixed well in 50 cm reaction coil Figure3. Salbutamol (1000 μg/mL) were prepared by dissolving 0.1 g of 100µL was injected into carrier stream which product thiosemicarbazide in distilled water and dilution to the from mixing three channel the first channel carrier (0.2) mark in 100mL volumetric flask. M 4-nitrophenyl hydrazine the mixed react with oxidative -preparation 1 M NaOH was prepared by dissolving 10 g agent 0.1 M KIO3, then the mixture reacts with third of NaOH in 250 mL distilled water, 4-nitro phenyl channel stream 2 M NaOH the product carryout via hydrazine 0.2M was prepared by dissolving 3.06g in 2mL mixed well 50 cm reaction coil Figure4, the resulting of of concentrated Sulfuric acid in 100mL distilled water, Methyldopa and Salbutamol dark green and violet at λ max 0.1 M KIO3 was prepared by dissolving 2.14 g of KIO3 in (460 ,530) nm respectively.
Recommended publications
  • TR-348: Alpha-Methyldopa Sesquihydrate (CASRN 41372-08-1)
    NATIONAL TOXICOLOGY PROGRAM Technical Report Series No. 348 TOXICOLOGY AND CARCINOGENESIS STUDIES OF a/pha-METHYLDOPA SESQUIHYDRATE (CAS NO. 41372-08-1) IN F344/N RATS AND B6C3Fi MICE (FEED STUDIES) U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health NTP TECHNICAL REPORT ON THE TOXICOLOGY AND CARCINOGENESIS STUDIES OF a/p/)a-METHYLDOPA SESQUIHYDRATE (CAS NO. 41372-08-1) IN F344/N RATS AND B6C3Fi MICE (FEED STUDIES) June K. Dunnick, Ph.D., Chemical Manager NATIONAL TOXICOLOGY PROGRAM P.O. Box 12233 Research Triangle Park, NC 27709 March 1989 NTP TR 348 NIH Publication No. 89-2803 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health NOTE TO THE READER This study was performed under the direction of the K’ational Institute of Environmental Health Sci- ences as a function of the National Toxicology Program. The studies described in this Technical Re- port have been conducted in compliance with NTP chemical health and safety requirements and must meet or exceed all applicable Federal, state, and local health and safety regulations. Animal care and use were in accordance with the U.S. Public Health Service Policy on Humane Care and Use of Ani- mals. All NTP toxicology and carcinogenesis studies are subjected to a data audit before being pre- sented for public peer review. Although every effort is made to prepare the Technical Reports as accurately as possible, mistakes may occur. Readers are requested to identify any mistakes so that corrective action may be taken. Further, anyone who is aware of related ongoing or published studies not mentioned in this report is encouraged to make this information known to the NTP.
    [Show full text]
  • United States Patent (10) Patent No.: US 8,969,514 B2 Shailubhai (45) Date of Patent: Mar
    USOO896.9514B2 (12) United States Patent (10) Patent No.: US 8,969,514 B2 Shailubhai (45) Date of Patent: Mar. 3, 2015 (54) AGONISTS OF GUANYLATECYCLASE 5,879.656 A 3, 1999 Waldman USEFUL FOR THE TREATMENT OF 36; A 6. 3: Watts tal HYPERCHOLESTEROLEMIA, 6,060,037- W - A 5, 2000 Waldmlegand et al. ATHEROSCLEROSIS, CORONARY HEART 6,235,782 B1 5/2001 NEW et al. DISEASE, GALLSTONE, OBESITY AND 7,041,786 B2 * 5/2006 Shailubhai et al. ........... 530.317 OTHER CARDOVASCULAR DISEASES 2002fOO78683 A1 6/2002 Katayama et al. 2002/O12817.6 A1 9/2002 Forssmann et al. (75) Inventor: Kunwar Shailubhai, Audubon, PA (US) 2003,2002/0143015 OO73628 A1 10/20024, 2003 ShaubhaiFryburg et al. 2005, OO16244 A1 1/2005 H 11 (73) Assignee: Synergy Pharmaceuticals, Inc., New 2005, OO32684 A1 2/2005 Syer York, NY (US) 2005/0267.197 A1 12/2005 Berlin 2006, OO86653 A1 4, 2006 St. Germain (*) Notice: Subject to any disclaimer, the term of this 299;s: A. 299; NS et al. patent is extended or adjusted under 35 2008/0137318 A1 6/2008 Rangarajetal.O U.S.C. 154(b) by 742 days. 2008. O151257 A1 6/2008 Yasuda et al. 2012/O196797 A1 8, 2012 Currie et al. (21) Appl. No.: 12/630,654 FOREIGN PATENT DOCUMENTS (22) Filed: Dec. 3, 2009 DE 19744O27 4f1999 (65) Prior Publication Data WO WO-8805306 T 1988 WO WO99,26567 A1 6, 1999 US 2010/O152118A1 Jun. 17, 2010 WO WO-0 125266 A1 4, 2001 WO WO-02062369 A2 8, 2002 Related U.S.
    [Show full text]
  • NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Amphetamine and Methamphetamine
    Published 2005 Wiley-Liss, Inc.w Birth Defects Research (Part B) 74:471–584 (2005) NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity Of Amphetamine and Methamphetamine Mari Golub,1 Lucio Costa,2 Kevin Crofton,3 Deborah Frank,4 Peter Fried,5 Beth Gladen6 Rogene Henderson,7 Erica Liebelt,8 Shari Lusskin,9 Sue Marty,10 Andrew Rowland11 John Scialli12 and Mary Vore13 1California Environment Protection Agency, Sacramento, California 2University of Washington, Seattle, Washington 3U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 4Boston Medical Center, Boston, Massachusetts 5Carleton University, Ottawa, Ontario 6National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 7Lovelace Respiratory Research Institute, Albuquerque, New Mexico 8University of Alabama at Birmingham School of Medicine, Birmingham, Alabama 9New York University School of Medicine, New York, New York 10The Dow Chemical Company, Midland, Michigan 11University of New Mexico, Albuquerque, New Mexico 12Phoenix, Arizona 13University of Kentucky, Lexington, Kentucky PREFACE studies indexed before December 31, 2004. References were also identified from databases such as REPRO- The National Toxicology Program (NTP) and the TOXs, HSDB, IRIS, and DART and from report National Institute of Environmental Health Sciences bibliographies. (NIEHS) established the NTP Center for the Evaluation This evaluation resulted from the efforts of a 13- of Risks to Human Reproduction (CERHR) in June 1998. member panel of government and non-government The purpose of the Center is to provide timely, unbiased, scientists that culminated in a public expert panel scientifically sound evaluations of human and experi- meeting held January 10–12, 2005. This report is a mental evidence for adverse effects on reproduction and product of the Expert Panel and is intended to (1) development caused by agents to which humans may be interpret the strength of scientific evidence that exposed.
    [Show full text]
  • Summary of Product Characteristics
    Health Products Regulatory Authority Summary of Product Characteristics 1 NAME OF THE MEDICINAL PRODUCT Salbutamol CFC-Free Inhaler 100 micrograms per metered dose, pressurised inhalation, suspension 2 QUALITATIVE AND QUANTITATIVE COMPOSITION One metered dose contains 100 micrograms of salbutamol (equivalent to 120 micrograms of salbutamol sulphate). This is equivalent to a delivered dose of 90 micrograms of salbutamol (equivalent to 108 micrograms of salbutamol sulphate). For the full list of excipients, see section 6.1. 3 PHARMACEUTICAL FORM Pressurised inhalation suspension Pressurised inhalation suspension supplied in an aluminium canister with a metering valve and a plastic actuator and dust cap. 4 CLINICAL PARTICULARS 4.1 Therapeutic Indications Salbutamol CFC-Free Inhaler is indicated in adults, adolescents and children. For babies and children under 4 years of age, see sections 4.2 and 5.1. Salbutamol CFC-Free Inhaler is indicated for the relief and prevention of bronchial asthma and conditions associated with reversible airways obstruction. Salbutamol CFC-Free Inhaler can be used as relief medication in the management of mild, moderate or severe asthma, provided that its use does not delay the introduction and use of regular inhaled corticosteroid therapy, where necessary. 4.2 Posology and method of administration Salbutamol CFC-Free Inhaler is for oral inhalation use only. Posology Adults (including the elderly) and adolescents (children 12 years and over): For the relief of acute bronchospasm, one inhalation (100 micrograms) increasing to two inhalations (200 micrograms), if necessary. To prevent allergen- or exercise-induced symptoms, two inhalations (200 micrograms) should be taken 10-15 minutes before challenge. Maximum daily dose: two inhalations (200 micrograms) up to four times a day.
    [Show full text]
  • Supporting Information a Analysed Substances
    Electronic Supplementary Material (ESI) for Analyst. This journal is © The Royal Society of Chemistry 2020 List of contents: Tab. A1 Detailed list and classification of analysed substances. Tab. A2 List of selected MS/MS parameters for the analytes. Tab. A1 Detailed list and classification of analysed substances. drug of therapeutic doping agent analytical standard substance abuse drug (WADA class)* supplier (+\-)-amphetamine ✓ ✓ S6 stimulants LGC (+\-)-methamphetamine ✓ S6 stimulants LGC (+\-)-3,4-methylenedioxymethamphetamine (MDMA) ✓ S6 stimulants LGC methylhexanamine (4-methylhexan-2-amine, DMAA) S6 stimulants Sigma cocaine ✓ ✓ S6 stimulants LGC methylphenidate ✓ ✓ S6 stimulants LGC nikethamide (N,N-diethylnicotinamide) ✓ S6 stimulants Aldrich strychnine S6 stimulants Sigma (-)-Δ9-tetrahydrocannabinol (THC) ✓ ✓ S8 cannabinoids LGC (-)-11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) S8 cannabinoids LGC morphine ✓ ✓ S7 narcotics LGC heroin (diacetylmorphine) ✓ ✓ S7 narcotics LGC hydrocodone ✓ ✓ Cerillant® oxycodone ✓ ✓ S7 narcotics LGC (+\-)-methadone ✓ ✓ S7 narcotics Cerillant® buprenorphine ✓ ✓ S7 narcotics Cerillant® fentanyl ✓ ✓ S7 narcotics LGC ketamine ✓ ✓ LGC phencyclidine (PCP) ✓ S0 non-approved substances LGC lysergic acid diethylamide (LSD) ✓ S0 non-approved substances LGC psilocybin ✓ S0 non-approved substances Cerillant® alprazolam ✓ ✓ LGC clonazepam ✓ ✓ Cerillant® flunitrazepam ✓ ✓ LGC zolpidem ✓ ✓ LGC VETRANAL™ boldenone (Δ1-testosterone / 1-dehydrotestosterone) ✓ S1 anabolic agents (Sigma-Aldrich)
    [Show full text]
  • Colorimetric Approaches to Drug Analysis and Applications – a Review
    REVIEW ARTICLE Am. J. PharmTech Res. 2019; 9(01) ISSN: 2249-3387 Journal home page: http://www.ajptr.com/ Colorimetric Approaches To Drug Analysis And Applications – A Review Sowjanya Gummadi*, Mohana Kommoju Department of Pharmaceutical Analysis, Institute of Pharmacy, GITAM (Deemed to be University), Visakhapatnam-530045, Andhra Pradesh, India ABSTRACT The main purpose of this review is to highlight the importance of colorimetric approaches to drug analysis both in dosage forms as well as biological samples. Colorimetric methods using colorimetric reagents are highly sensitive, specific and an easy way of determining various analytes in a variety of matrices within a short time. The colorimetric procedures discussed are statistically validated and reported in various quality control laboratories. Hence in the present review significance of colorimetric procedures, various reagents used along with principles and applications are mentioned. Key words: Colorimetric approaches, sensitive, matrices, quality control, applications. *Corresponding Author Email: [email protected] Received 01 November 2018, Accepted 23 December 2018 Please cite this article as: Gummadi S et al., Colorimetric Approaches To Drug Analysis And Applications – A Review. American Journal of PharmTech Research 2019. Gummadi et. al., Am. J. PharmTech Res. 2019; 9(01) ISSN: 2249-3387 INTRODUCTION Colorimetry is a technique which involves the quantitative estimation of colors frequently used in biochemical investigation. Color can be produced by any substance when it binds with color forming chromogens. The difference in color intensity results in difference in the absorption of light. The intensity of color is directly proportional to the concentration of the compound being measured.1 Wavelength between 380 nm to 780 nm forms the visible band of light in electromagnetic spectrum.
    [Show full text]
  • Experimental and Molecular Dynamics Simulation Studies of Partitioning and Transport Across Lipid Bilayer Membranes
    University of Kentucky UKnowledge University of Kentucky Doctoral Dissertations Graduate School 2009 EXPERIMENTAL AND MOLECULAR DYNAMICS SIMULATION STUDIES OF PARTITIONING AND TRANSPORT ACROSS LIPID BILAYER MEMBRANES Ravindra Wadhumal Tejwani University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Tejwani, Ravindra Wadhumal, "EXPERIMENTAL AND MOLECULAR DYNAMICS SIMULATION STUDIES OF PARTITIONING AND TRANSPORT ACROSS LIPID BILAYER MEMBRANES" (2009). University of Kentucky Doctoral Dissertations. 738. https://uknowledge.uky.edu/gradschool_diss/738 This Dissertation is brought to you for free and open access by the Graduate School at UKnowledge. It has been accepted for inclusion in University of Kentucky Doctoral Dissertations by an authorized administrator of UKnowledge. For more information, please contact [email protected]. ABSTRACT OF DISSERTATION Ravindra Wadhumal Tejwani The Graduate School University of Kentucky 2009 EXPERIMENTAL AND MOLECULAR DYNAMICS SIMULATION STUDIES OF PARTITIONING AND TRANSPORT ACROSS LIPID BILAYER MEMBRANES ABSTRACT OF DISSERTATION A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the College of Pharmacy at the University of Kentucky By Ravindra Wadhumal Tejwani Lexington, Kentucky Director: Dr. Bradley D. Anderson, Professor of Pharmaceutical Sciences Lexington, Kentucky 2009 Copyright © Ravindra W. Tejwani 2009 ABSTRACT OF DISSERTATION EXPERIMENTAL AND MOLECULAR DYNAMICS SIMULATION STUDIES OF PARTITIONING AND TRANSPORT ACROSS LIPID BILAYER MEMBRANES Most drugs undergo passive transport during absorption and distribution in the body. It is desirable to predict passive permeation of future drug candidates in order to increase the productivity of the drug discovery process.
    [Show full text]
  • Prodrugs Design Based on Inter- and Intramolecular Chemical Processes
    Chem Biol Drug Des 2013; 82: 643–668 Review Prodrugs Design Based on Inter- and Intramolecular Chemical Processes Rafik Karaman1,2,* compound satisfies a number of preset criteria to start clinical development. The number of years it takes to intro- 1Bioorganic Chemistry Department, Faculty of Pharmacy, duce a drug to the pharmaceutical market is over 10 years Al-Quds University, P.O. Box 20002, Jerusalem, Palestine with a cost of more than $1 billion dollars (1,2). 2Department of Science, University of Basilicata, Via dell’Ateneo Lucano 10, 85100, Potenza, Italy Modifying the absorption, distribution, metabolism, and *Corresponding author: Rafik Karaman, elimination (ADME) properties of an active drug requires a [email protected] complete understanding of the physicochemical and bio- logical behavior of the drug candidate (3 6). This includes This review provides the reader a concise overview of – the majority of prodrug approaches with the emphasis comprehensive evaluation of drug-likeness involving on the modern approaches to prodrug design. The prediction of ADME properties. These predictions can be chemical approach catalyzed by metabolic enzymes attempted at several levels: in vitro–in vivo using data which is considered as widely used among all other obtained from tissue or recombinant material from human approaches to minimize the undesirable drug physico- and preclinical species, and in silico or computational pre- chemical properties is discussed. Part of this review dictions projecting in vitro or in vivo data, involving the will shed light on the use of molecular orbital methods evaluation of various ADME properties, using computa- such as DFT, semiempirical and ab initio for the design tional approaches such as quantitative structure activity of novel prodrugs.
    [Show full text]
  • The 2013 "Research on Drug Evidence"
    The 2013 “Research on Drug Evidence” Report [From the 17th ICPO / INTERPOL Forensic Science Symposium] Robert F. X. Klein U.S. Department of Justice Drug Enforcement Administration Special Testing and Research Laboratory 22624 Dulles Summit Court Dulles, VA 20166 [[email protected]] ABSTRACT: A reprint of the 2013 “Research on Drug Evidence” Report (a review) is provided. KEYWORDS: INTERPOL, Illicit Drugs, Controlled Substances, Forensic Chemistry. Important Information: Distributed at the 17th ICPO / INTERPOL Forensic Science Symposium, Lyon, France, October 8 - 10, 2013.* Authorized Reprint. Copyright INTERPOL. All rights reserved. May not be reprinted without express permission from INTERPOL. For pertinent background, see: Klein RFX. ICPO / INTERPOL Forensic Science Symposia, 1995 - 2016. “Research on Drug Evidence”. Prefacing Remarks (and a Request for Information). Microgram Journal 2016;13(1-4):1-3. Citations in this report from the Journal of the Clandestine Laboratory Investigating Chemists Association were (and remain) Law Enforcement Restricted. The "General Overview" (Talking Paper) was removed from this reprint (Editor's discretion). This reprint is derived from the original electronic document, and is not an image of the best available hard copy (as was utilized for the 1995 and 1998 reports). For this reason, the pagination in the Proceedings is not retained in this reprint, some minor reformatting was done to eliminate deadspace, and all widow and orphan lines were left as is. [* Due to travel restrictions in effect in late 2013, this report and the associated "General Overview" (Talking Paper) was not actually presented, but rather the report was only distributed to the attendees.] Microgram Journal 2016, Volume 13; Numbers 1-4 511 Research on Drug Evidence January 1, 2010 - June 30, 2013 Presented by: Jeffrey H.
    [Show full text]
  • Annex 2B Tariff Schedule of the United States See General Notes to Annex 2B for Staging Explanation HTSUS No
    Annex 2B Tariff Schedule of the United States See General Notes to Annex 2B for Staging Explanation HTSUS No. Description Base Rate Staging 0101 Live horses, asses, mules and hinnies: 0101.10.00 -Purebred breeding animals Free E 0101.90 -Other: 0101.90.10 --Horses Free E 0101.90.20 --Asses 6.8% B --Mules and hinnies: 0101.90.30 ---Imported for immediate slaughter Free E 0101.90.40 ---Other 4.5% A 0102 Live bovine animals: 0102.10.00 -Purebred breeding animals Free E 0102.90 -Other: 0102.90.20 --Cows imported specially for dairy purposes Free E 0102.90.40 --Other 1 cent/kg A 0103 Live swine: 0103.10.00 -Purebred breeding animals Free E -Other: 0103.91.00 --Weighing less than 50 kg each Free E 0103.92.00 --Weighing 50 kg or more each Free E 0104 Live sheep and goats: 0104.10.00 -Sheep Free E 0104.20.00 -Goats 68 cents/head A 0105 Live poultry of the following kinds: Chickens, ducks, geese, turkeys and guineas: -Weighing not more than 185 g: 0105.11.00 --Chickens 0.9 cents each A 0105.12.00 --Turkeys 0.9 cents each A 0105.19.00 --Other 0.9 cents each A -Other: 0105.92.00 --Chickens, weighing not more than 2,000 g 2 cents/kg A 0105.93.00 --Chickens, weighing more than 2,000 g 2 cents/kg A 0105.99.00 --Other 2 cents/kg A 0106 Other live animals: -Mammals: 0106.11.00 --Primates Free E 0106.12.00 --Whales, dolphins and porpoises (mammals of the order Cetacea); manatees and dugongs (mammals of the order Sirenia) Free E 0106.19 --Other: 2B-Schedule-1 HTSUS No.
    [Show full text]
  • Orciprenaline Sulphate (Alupent): Planned Withdrawal from the UK Market Following a Risk-Benefit Analysis
    MHRA PUBLIC ASSESSMENT REPORT Orciprenaline sulphate (Alupent): planned withdrawal from the UK market following a risk-benefit analysis November 2009 Executive summary 2 1. Introduction 3 2. Summary of data 3 2.1 Clinical pharmacology 3 2.2 Efficacy 3 2.3 Safety 4 3. Conclusions 8 4. References 9 5. Glossary 10 1 EXECUTIVE SUMMARY (Please note that this summary is intended to be accessible to all members of the public, including health professionals) Background The Medicines and Healthcare products Regulatory Agency (MHRA) is the government agency responsible for regulating the effectiveness and safety of medicines and medical devices in the UK. We continually review the safety of all medicines in the UK, and inform healthcare professionals and the public of the latest safety updates. In our Public Assessment Reports, we discuss the evidence for a safety issue with a particular drug or drug class, and changes made to the product information for the drug on the basis of this evidence, which will help safeguard public health. This MHRA Public Assessment Report discusses a review of the risks and benefits of a medicine called orciprenaline sulphate. Orciprenaline sulphate is available for oral administration as a syrup used to treat reversible airways obstructiona, which is a symptom of asthmab and chronic obstructive pulmonary diseasec. It acts on specific areas in the body called β- receptors, which relaxes the muscles used for breathing and opens the airways in the lungs. Orciprenaline sulphate was licensed in 1972 and is marketed in the UK under the brand name Alupent Syrup. As with any medicine, the use of orciprenaline sulphate may lead to adverse reactions (side-effects) in some individuals, which are described in the product information, including the patient information leaflet (see the Electronic Medicines Compendium (product information) website).
    [Show full text]
  • The Organic Chemistry of Drug Synthesis
    The Organic Chemistry of Drug Synthesis VOLUME 2 DANIEL LEDNICER Mead Johnson and Company Evansville, Indiana LESTER A. MITSCHER The University of Kansas School of Pharmacy Department of Medicinal Chemistry Lawrence, Kansas A WILEY-INTERSCIENCE PUBLICATION JOHN WILEY AND SONS, New York • Chichester • Brisbane • Toronto Copyright © 1980 by John Wiley & Sons, Inc. All rights reserved. Published simultaneously in Canada. Reproduction or translation of any part of this work beyond that permitted by Sections 107 or 108 of the 1976 United States Copyright Act without the permission of the copyright owner is unlawful. Requests for permission or further information should be addressed to the Permissions Department, John Wiley & Sons, Inc. Library of Congress Cataloging in Publication Data: Lednicer, Daniel, 1929- The organic chemistry of drug synthesis. "A Wiley-lnterscience publication." 1. Chemistry, Medical and pharmaceutical. 2. Drugs. 3. Chemistry, Organic. I. Mitscher, Lester A., joint author. II. Title. RS421 .L423 615M 91 76-28387 ISBN 0-471-04392-3 Printed in the United States of America 10 987654321 It is our pleasure again to dedicate a book to our helpmeets: Beryle and Betty. "Has it ever occurred to you that medicinal chemists are just like compulsive gamblers: the next compound will be the real winner." R. L. Clark at the 16th National Medicinal Chemistry Symposium, June, 1978. vii Preface The reception accorded "Organic Chemistry of Drug Synthesis11 seems to us to indicate widespread interest in the organic chemistry involved in the search for new pharmaceutical agents. We are only too aware of the fact that the book deals with a limited segment of the field; the earlier volume cannot be considered either comprehensive or completely up to date.
    [Show full text]