DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 9,347,961 B2 Karlsen Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 9,347,961 B2 Karlsen Et Al US009347961 B2 (12) United States Patent (10) Patent No.: US 9,347,961 B2 Karlsen et al. (45) Date of Patent: May 24, 2016 (54) TEST KIT FOR THE QUANTITATIVE 2008/0058351 A1* 3/2008 Tung ..................... CO7B 59,002 514,259.3 DETERMINATION OF NARCOTC DRUGS 2008/0287.495 A1 * 1 1/2008 Tung .................... CO7D 317.64 514,321 (71) Applicant: CHIRONAS. Trondheim (NO) 2009.006870.6 A1 3/2009 Freudenschluss ......... C12P1/02 435,713 (72) Inventors: Morten Salihi Karlsen, Trondheim 2009/0093.422 A1* 4/2009 Tung .................... CO7D :S. (NO), Huiling Liu, Trondheim (NO); 2009/0208413 A1* 8, 2009 Reis ..................... CO7D 243/24 Jon Eigill Johansen, Tiller (NO) 424f1.81 2009/0291 152 A1* 1 1/2009 Tung .................... CO7D 417/12 (73) Assignee: CHIRONAS. Trondheim (NO) 424,722 2010/0130723 A1* 5, 2010 Latham .................... CO7K 1/10 c - r - 530/342 ( ) Notice: Subject tO any disclaimer, the term of this 2012. O156139 A1 ck 6, 2012 Katz-Birull . A61 K 31 136 patent is extended or adjusted under 35 4249.3 U.S.C. 154(b) by 0 days. 2014/0227792 A1* 8, 2014 Johansen ............. A61K 31,137 436.8 (21) Appl. No.: 14/414,146 FOREIGN PATENT DOCUMENTS (22) PCT Filed: Jul.19, 2013 EP 2551675 A1 1, 2013 JP 2008266.149 A * 11 2008 (86). PCT No.: PCT/EP2013/065.323 WO 2004.056398 A1 T 2004 WO 2006091885 A2 8, 2006 S371 (c)(1), WO 201102415.6 A1 3, 2011 (2) Date: Jan. 12, 2015 OTHER PUBLICATIONS (87) PCT Pub. No.: WO2014/013063 Thomas Berget al: “C labelled internal standards.A solution to mini PCT Pub. Date: Jan. 23, 2014 mize ion Suppression effects in liquid chromatographytandem mass spectrometry analyses of drugs in biological samples?'. Journal of (65) Prior Publication Data Chromatography, Elsevier Science Publishers B.V. NL, vol. 1218, No. 52, Oct. 26, 2011, pp. 9366-9374. US 2015/0204893 A1 Jul. 23, 2015 Marie Kjaergaard Bjork et al: “Determination of 19 drugs of abuse and metabolites in whole blood by high-performance liquid (30) Foreign Application Priority Data chromatogarphya tandem mass spectrometry. Analytical and Bioanalytical Chemistry, Springer, Berlin, DE, vol. 396, No. 7, Nov. 18, 2009, pp. 2393-2401. Jul. 19, 2012 (EP) ..................................... 121771.25 Ceder Gunnel et al: “Concentrations of Unconjugated Morphine, Codeine and 6-Acetylmorphine in Urine Specimens From Suspected (51) Int. Cl. Drugged Drivers', Journal of Forensic Sciences, Callaghan and CO, HOIJ 49/00 (2006.01) Chicago, IL, US, vol. 47, No. 2, Jan. 1, 2002, pp. 366-368. GOIN33/94 (2006.01) Wei-Tun Changetal:"13C4-Secobarbital as the Internal Standard for the Quantitative Determination of Secobarbital-A Critical Evalua GOIN30/72 (2006.01) tion”. J. Forensic Sci., vol. 45, No. 3, Jan. 1, 2000, pp. 659-664. (52) U.S. Cl. CPC ................ G0IN33/94 (2013.01); G0IN30/72 (Continued) (2013.01); G0IN33/946 (2013.01) (58) Field of Classification Search Primary Examiner — Andrew Smyth None (74) Attorney, Agent, or Firm — Abel Law Group, LLP See application file for complete search history. (57) ABSTRACT (56) References Cited A test kit for the quantitative determination of narcotic drugs comprising (A) series of sealed vessels, each vessel contain U.S. PATENT DOCUMENTS inga deuterium free isotopologue of a narcotic drug in exactly defined concentrations and quantities, wherein the isotopo 8,455,619 B2 * 6/2013 Latham .................... CO7K 1.02 530.333 logue differs from Vessel to vessel and—wherein the quanti 8,703,099 B2 * 4/2014 Reis ..................... CO7D 243/24 ties of the isotopologue differ from vessel to vessel or are the 4249.1 same for all vessels; and/or (B) series of sealed vessels, each 8,796.267 B2 * 8/2014 Tung .......................... 514/2312 vessel containing in exactly defined concentrations and quan 2006/028.1776 A1* 12, 2006 Giribone ............ A61K 51,0455 tities the same isotopologue in quantities which differ from 514,283 2007/0037815 A1* 2/2007 Tung ................ CO7D 317,54 vessel to vessel; wherein the free isotopologues are selected 514,249 from narcotic drugs; prodrugs, salts, Solvates, hydrates and 2007/0066657 A1* 3/2007 Tung ................ CO7D401 12 polymorphs and contain at least three stable isotopes selected 514/326 from the group consisting of 'C, 'NandO in the molecule 2007/0116643 A1* 5/2007 Tung ..................... CO7B 59,002 423,647.7 with a degree of labeling of at least 95 mol-%; the use of the 2007/0191432 A1* 8/2007 Tung .................... CO7D 317.64 test kit and a method for quantitatively determining narcotic 514,320 drugs. 2007/0276001 A1* 1 1/2007 Tung .................... CO7D401 12 514/326 20 Claims, No Drawings US 9,347,961 B2 Page 2 (56) References Cited Singh Get al: “A validated stable isotope dilution liquid chromatog raphy tandem mass spectrometry assay for the trace analysis of OTHER PUBLICATIONS cocaine and its major metabolites in plasma'. Analytical Chemistry, American Chemical Society, US, vol. 71, No. 10, May 15, 1999, pp. Ray H. Liu et al: “Peer Reviewed: Isotopically Labeled Analogues for 2021-2027 Drug Quantitation'. Analytical Chemistry, vol. 74, No. 23, Dec. 1, Wang S M et al: "Simultaneous determination of amphetamine and 2002, pp. 618 A-626 A. methamphetamine enantiomers in urine by simultaneous liquid-liq Wei-Tun Chang et al: “Mechanistic Studies on the Use of 2H- and uid extraction and diastereomeric derivatization followed by gas 13C-Analogues as Internal Standards in Selected Ion Monitoring chromatographic-isotope dilution mass spectrometry. Journal of GC-MS Quantitative Determination—Butalbitai Example'. Journal Chromatography B: Biomedical Sciences & Applications, Elsevier, of Analytical Toxicology, vol. 25, Jan. 1, 2001, pp. 659-669. Amsterdam, NL, vol. 816, No. 1-2, Feb. 2005, pp. 131-143. Rodger L. Foltz et al: "GC/MS Assays for Abused Drugs in Body Fluids”, NIDARES MONOGR., vol. 32, Jan. 1, 1980, pp. pp. 1-214. * cited by examiner US 9,347,961 B2 1. 2 TEST KIT FOR THE QUANTITATIVE hallucinogens, including psychedelics, dissociatives and DETERMINATION OF NARCOTC DRUGS deliriants has become a worldwide major concern and has a tremendous The present invention relates to a novel test kit for the negative social, criminal and economical impact in all Soci quantitative determination of narcotic drugs containing at eties. In particular, the highly addictive 2-phenylethylamine least one deuterium free labeled, in particular C labeled, hallucinogens and/or stimulants such as amphetamine, meth isotopologue of a narcotic drug. amphetamine and ecstasy are consumed in ever-growing Furthermore, the present invention relates to the use of the amounts. Therefore, it would be particularly desirable to have novel test kits in chemical analysis and metabolic Studies. compounds of this type available that are labeled with 'C 10 and, optionally, with 'N and/or "O, however, not in combi Additionally, the present invention relates to a novel ana nation with deuterium, in order to have reliable standards for lytical method for the determination of narcotic drugs. the chemical analysis of Such illegal psychotropic, narcotic drugs at hand. CITED DOCUMENTS Sigma-Aldrich and Cambridge Isotope Laboratories offer 15 'Co'N-phenylalanine, Cambridge Isotope Laboratories The documents cited in the present application are incor offers 'Co-phenylalanine and 'CI-, 'Co- and porated by reference in their entirety. 'Co'N-tyrosine and Sigma-Aldrich offers "Cal-ritalinic acid. The compounds are used for tandem MS standards. DESCRIPTION OF THE PRIOR ART However, the compounds are not narcotic drugs, and, there fore, cannot serve as standards for their analysis. Chemical analysis of pharmaceuticals and legal and illegal In the article of I. A. Low, R. H. Liu, M. G. Legendre, E. G. drugs and their metabolites and impurities can be performed Piotrowski and R. L. Furner in Biomedical & Environmental by any method applying combinations of gas chromatogra Mass Spectrometry (1986), 13 (10), 531-534, the use of a phy (GC), liquid chromatography (LC), ultra performance methamphetamine containing only one 'C-carbon atom is liquid chromatography (UPLC), mass spectrometry (MC), 25 described in the mass spectrometry analysis. tandem mass spectrometry (MC/MC) and/or nuclear mag The article of R. S. Hsi and L. S. Stelzer, Synthesis of netic resonance spectroscopy (NMR), as for example, GC Adinazolam multiply labeled with Carbon-13 and Deute MS, GC-MS/MS, LC-MS, LC-MS/MS, UPLC-MS, UPLC rium, in Journal of Labelled Compounds in Radiopharmaceu MS/MS, UPLC-MS/MS, LC-NMR and UPLC-NMR. ticals, Volume XXVII, No. 3, 287-295, 1989, describes the Internal standards are used to determine the level or quan 30 synthesis and the spectroscopic properties of "Cal-adina tity of each analyte in the sample. Traditionally, such an Zolam. However, no test kits are disclosed. analysis is performed using deuterium labeling of the analyte. Berget al. (J. Chrom. Vol. 1218, no. 52,9366) describes the However, disadvantages associated with deuterium labeling use of "C-methamphetamine as internal standard. are the risk of exchange, i.e. deuterium and hydrogen can be The Japanese patent application JP 2008–266149 A dis exchanged in the workup procedure, and different elution 35 closes estradiol with a 'C-benzene ring and various times, i.e. the deuterium labeled compounds elute differently Co-precursors such as "Cal-benzene, -nitrobenzene, -io from the native, unlabeled compounds both in GC and in LC. donitrobenzene, -iodoaniline, -iodophenol and -iodoanisol. In addition, the deuterium labeled compounds may have a However, "Cal-estradiol is no narcotic drug and, therefore, response factor which is slightly different from the response it cannot serve as a standard for the chemical analysis of factor of the native, unlabeled compounds. 40 narcotic drugs. The C isotope labeled internal standards are particularly The article by A. Weis and S. P. Markey “Synthesis of suitable of minimizing the effects of ion suppression effects D/L-Norepinephrine-U-'C)” in Journal of Labelled Com in LC-MS/MS analysis, therefore the quantitative analysis in pounds and Radiopharmaceuticals, volume XXV, No.
Load more

Recommended publications
  • Psychedelic Resource List.Pdf
    A Note from the Author… The Psychedelic Resource List (PRL) was born in 1994 as a subscription-based newsletter. In 1996, everything that had previously been published, along with a bounty of new material, was updated and compiled into a book. From 1996 until 2004, several new editions of the book were produced. With each new version, a decrease in font size correlated to an increase in information. The task of revising the book grew continually larger. Two attempts to create an updated fifth edition both fizzled out. I finally accepted that keeping on top of all of the new books, businesses, and organizations, had become a more formidable challenge than I wished to take on. In any case, these days folks can find much of what they are looking for by simply using an Internet search engine. Even though much of the PRL is now extremely dated, it occurred to me that there are two reasons why making it available on the web might be of value. First, despite the fact that a good deal of the book’s content describes things that are no longer extant, certainly some of the content relates to writings that are still available and businesses or organizations that are still in operation. The opinions expressed regarding such literature and groups may remain helpful for those who are attempting to navigate the field for solid resources, or who need some guidance regarding what’s best to avoid. Second, the book acts as a snapshot of underground culture at a particular point in history. As such, it may be found to be an enjoyable glimpse of the psychedelic scene during the late 1990s and early 2000s.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 De Juan Et Al
    US 200601 10428A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 de Juan et al. (43) Pub. Date: May 25, 2006 (54) METHODS AND DEVICES FOR THE Publication Classification TREATMENT OF OCULAR CONDITIONS (51) Int. Cl. (76) Inventors: Eugene de Juan, LaCanada, CA (US); A6F 2/00 (2006.01) Signe E. Varner, Los Angeles, CA (52) U.S. Cl. .............................................................. 424/427 (US); Laurie R. Lawin, New Brighton, MN (US) (57) ABSTRACT Correspondence Address: Featured is a method for instilling one or more bioactive SCOTT PRIBNOW agents into ocular tissue within an eye of a patient for the Kagan Binder, PLLC treatment of an ocular condition, the method comprising Suite 200 concurrently using at least two of the following bioactive 221 Main Street North agent delivery methods (A)-(C): Stillwater, MN 55082 (US) (A) implanting a Sustained release delivery device com (21) Appl. No.: 11/175,850 prising one or more bioactive agents in a posterior region of the eye so that it delivers the one or more (22) Filed: Jul. 5, 2005 bioactive agents into the vitreous humor of the eye; (B) instilling (e.g., injecting or implanting) one or more Related U.S. Application Data bioactive agents Subretinally; and (60) Provisional application No. 60/585,236, filed on Jul. (C) instilling (e.g., injecting or delivering by ocular ion 2, 2004. Provisional application No. 60/669,701, filed tophoresis) one or more bioactive agents into the Vit on Apr. 8, 2005. reous humor of the eye. Patent Application Publication May 25, 2006 Sheet 1 of 22 US 2006/0110428A1 R 2 2 C.6 Fig.
    [Show full text]
  • Download Book Sacred Journeys As
    Sa cred Jour neys: ©2015, 2016, 2017 Artscience Im ages: authors and friends, com pany and press pic- tures, PhotoDisc, Corel, Wikipedia, Mindlift Beeldbankiers. Dis tri bu tion: Boekencoöperatie Nederland u.a. email: [email protected] www.boekcoop.nl www.boekenroute.nl (webshop) All rights re served, in clud ing dig i tal re dis tri bu tion and ebook First editiion: De cem ber 2015, Sec ond, ap pended edition April 2016 Third edition Jan. 2017 ISBN 9789492079091 pub lisher: Onderstroomboven Collectief im print: Artscience. Pa perback price € 6,95 Con tents 1 Pre fa ce 7 2 Tripping: the process 10 Journey to the dream 10 The pre pa ra ti on 11 Pha ses, gig gling 13 Iso la ti on, li mi na li ty, the dark 14 Peak 19 Sit ters: de sig na ted hel pers 22 The mys ti cal, re gres si on 26 Rebirth and de ath 27 The end of the trip: co ming down 28 Over sti mu la ti on 29 The af ter-ef fects 30 3 Set and Set ting 32 Agen da 33 Pla ce 34 With whom, with what? 34 Bon ding and trans fe ren ce 35 Dif fe rent ways of using 36 4 Pur po se 37 Dee per goals 38 Over co ming fear 40 To le ran ce 41 5 Ri tu als and Group ses sions 42 He a ling jour neys, mys ti cal in sights 44 Me di cal use 45 Re pe ti ti on, loops 46 Stages of a ritu al 49 Ri tes of pas sa ge: ini ti a ti on 50 Contact – alignment - group mind 52 Struc tu re amidst cha os 54 To copy an existing ritu al or to crea te somet hing new 54 6 Sanc tu a ry, safe spa ce 57 Sa fe ty first 57 Sa cred spa ce, tem po ra ry au to no mous zone 58 Hol ding spa ce and cir cle in te gri ty 61 7 His to ry
    [Show full text]
  • United States Patent (10) Patent No.: US 8,916,581 B2 Boyd Et Al
    USOO891 6581 B2 (12) United States Patent (10) Patent No.: US 8,916,581 B2 Boyd et al. (45) Date of Patent: *Dec. 23, 2014 (54) (S)-N-METHYLNALTREXONE 4,194,045 A 3, 1980 Adelstein 4,203,920 A 5, 1980 Diamond et al. (75) Inventors: Thomas A. Boyd, Grandview, NY (US); 4,241,066 A 12, 1980 Kobylecki et al. H OW d Wagoner,goner, Warwick,s NY (US);s 4,311,833.4,277,605 A T.1/1982 1981 NamikoshiBuyniski et etal. al. Suketu P. Sanghvi, Kendall Park, NJ 4.322,426 A 3/1982 Hermann et al. (US); Christopher Verbicky, 4.326,074 A 4, 1982 Diamond et al. Broadalbin, NY (US); Stephen 4.326,075 A 4, 1982 Diamond et al. “. s 4,377.568 A 3/1983 Chopra et al. Andruski, Clifton Park, NY (US) 4.385,078 A 5/1983 Onda et al. 4.427,676 A 1/1984 White et al. (73) Assignee: Progenics Pharmaceuticals, Inc., 4,430,327 A 2, 1984 Frederickson et al. Tarrytown, NY (US) 4,452,775 A 6/1984 Kent 4,457,907 A 7/1984 Porteret al. (*) Notice: Subject to any disclaimer, the term of this 4,462.839 A 7/1984 McGinley et al. patent is extended or adjusted under 35 4,518.4334,466,968 A 5/19858, 1984 McGinleyBernstein et al. U.S.C. 154(b) by 344 days. 4,533,739 A 8/1985 Pitzele et al. This patent is Subject to a terminal dis- 4,606,9094,556,552 A 12/19858/1986 PorterBechgaard et al.
    [Show full text]
  • )&F1y3x PHARMACEUTICAL APPENDIX to THE
    )&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. Product CAS No. Product CAS No. ABAMECTIN 65195-55-3 ACTODIGIN 36983-69-4 ABANOQUIL 90402-40-7 ADAFENOXATE 82168-26-1 ABCIXIMAB 143653-53-6 ADAMEXINE 54785-02-3 ABECARNIL 111841-85-1 ADAPALENE 106685-40-9 ABITESARTAN 137882-98-5 ADAPROLOL 101479-70-3 ABLUKAST 96566-25-5 ADATANSERIN 127266-56-2 ABUNIDAZOLE 91017-58-2 ADEFOVIR 106941-25-7 ACADESINE 2627-69-2 ADELMIDROL 1675-66-7 ACAMPROSATE 77337-76-9 ADEMETIONINE 17176-17-9 ACAPRAZINE 55485-20-6 ADENOSINE PHOSPHATE 61-19-8 ACARBOSE 56180-94-0 ADIBENDAN 100510-33-6 ACEBROCHOL 514-50-1 ADICILLIN 525-94-0 ACEBURIC ACID 26976-72-7 ADIMOLOL 78459-19-5 ACEBUTOLOL 37517-30-9 ADINAZOLAM 37115-32-5 ACECAINIDE 32795-44-1 ADIPHENINE 64-95-9 ACECARBROMAL 77-66-7 ADIPIODONE 606-17-7 ACECLIDINE 827-61-2 ADITEREN 56066-19-4 ACECLOFENAC 89796-99-6 ADITOPRIM 56066-63-8 ACEDAPSONE 77-46-3 ADOSOPINE 88124-26-9 ACEDIASULFONE SODIUM 127-60-6 ADOZELESIN 110314-48-2 ACEDOBEN 556-08-1 ADRAFINIL 63547-13-7 ACEFLURANOL 80595-73-9 ADRENALONE
    [Show full text]
  • D. M. Turner - Table of Contents
    Sssshhhh!! Don't blow our Cover!! file:///C|/Documents%20and%20Settings/All%20Users/Docume...r%20-%20the%20essential%20psychedelic%20guide/cover.html4/14/2004 9:40:08 PM D. M. Turner - Table of Contents TABLE OF CONTENTS Publication Information Foreword to the HTML Edition - by Forbidden Donut Introduction A Brief History of Psychedelics - From the Creation of Gods to the Demise of Psychedelic Reverence in Modern Times Psychedelic Safety - Understanding the Tools I - Traditional Psychedelics LSD - Molecule of Perfection Psilocybin Mushrooms - The Extraterrestrial Infiltration of Earth? Mescaline: Peyote & San Pedro Cactus - Shamanic Sacraments II - Empathogens Ecstasy - The Heart Opening Psychedelic 2C-B - The Erotic Empathogen III - Exotic Highs of a Connoisseur DMT - Candy for the Mind file:///C|/Documents%20and%20Settings/All%20Users/Doc...%20-%20the%20essential%20psychedelic%20guide/toc.html (1 of 2)4/14/2004 9:40:34 PM D. M. Turner - Table of Contents Harmala Alkaloids - Link to the Ancient Spirits Ketamine - The Ultimate Psychedelic Journey Multiple Combinations - Cosmic Synergism Further Explorations - Where do we go from Here? DMT ~ Water Spirit - A Magical Link Psychedelic Reality - CydelikSpace Bibliography Purchasing The Essential Psychedelic Guide Back Cover Text file:///C|/Documents%20and%20Settings/All%20Users/Doc...%20-%20the%20essential%20psychedelic%20guide/toc.html (2 of 2)4/14/2004 9:40:34 PM D. M. Turner - Publication Information The Essential Psychedelic Guide - By D. M. Turner First Printing - September 1994 Copyright ©1994 by Panther Press ISBN 0-9642636-1-0 Library of Congress Catalog registration in progress Printed in the United States of America Cover art by Nick Philip, SFX Lab Illustrations on pages 31, 41, 45, and 59 by P.B.M.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 6,264,917 B1 Klaveness Et Al
    USOO6264,917B1 (12) United States Patent (10) Patent No.: US 6,264,917 B1 Klaveness et al. (45) Date of Patent: Jul. 24, 2001 (54) TARGETED ULTRASOUND CONTRAST 5,733,572 3/1998 Unger et al.. AGENTS 5,780,010 7/1998 Lanza et al. 5,846,517 12/1998 Unger .................................. 424/9.52 (75) Inventors: Jo Klaveness; Pál Rongved; Dagfinn 5,849,727 12/1998 Porter et al. ......................... 514/156 Lovhaug, all of Oslo (NO) 5,910,300 6/1999 Tournier et al. .................... 424/9.34 FOREIGN PATENT DOCUMENTS (73) Assignee: Nycomed Imaging AS, Oslo (NO) 2 145 SOS 4/1994 (CA). (*) Notice: Subject to any disclaimer, the term of this 19 626 530 1/1998 (DE). patent is extended or adjusted under 35 O 727 225 8/1996 (EP). U.S.C. 154(b) by 0 days. WO91/15244 10/1991 (WO). WO 93/20802 10/1993 (WO). WO 94/07539 4/1994 (WO). (21) Appl. No.: 08/958,993 WO 94/28873 12/1994 (WO). WO 94/28874 12/1994 (WO). (22) Filed: Oct. 28, 1997 WO95/03356 2/1995 (WO). WO95/03357 2/1995 (WO). Related U.S. Application Data WO95/07072 3/1995 (WO). (60) Provisional application No. 60/049.264, filed on Jun. 7, WO95/15118 6/1995 (WO). 1997, provisional application No. 60/049,265, filed on Jun. WO 96/39149 12/1996 (WO). 7, 1997, and provisional application No. 60/049.268, filed WO 96/40277 12/1996 (WO). on Jun. 7, 1997. WO 96/40285 12/1996 (WO). (30) Foreign Application Priority Data WO 96/41647 12/1996 (WO).
    [Show full text]
  • Comparison of the Use of Aqueous and Nonaqueous Buffers in Association with Cyclodextrin for the Chiral Separation of 3,4-Methyl
    3904 Electrophoresis 2005, 26, 3904–3909 Yu-San Huang1 Comparison of the use of aqueous and nonaqueous Chung-Chen Tsai1 Ju-Tsung Liu2 buffers in association with cyclodextrin for the Cheng-Huang Lin1 chiral separation of 3,4-methylenedioxymeth- 1Department of Chemistry, amphetamine and related compounds National Taiwan Normal University, A comparison of the use of aqueous and nonaqueous buffers in association with b-CD Taipei, Taiwan for the chiral separation of (R)- and (S)-3,4-methylenedioxymethamphetamine and 2Forensic Science Center, related compounds is described. The (R)- and (S)-isomers of 3,4-methylenedioxy- Military Police Command, Ministry of National Defense, methamphetamine (MDMA) and its major metabolite 3,4-methylenedioxy- Taipei, Taiwan amphetamine (MDA) were prepared. Under aqueous and nonaqueous buffer condi- tions and based on the CZE and MEKC modes, the order of migration of (R)-MDA, (S)-MDA, (R)-MDMA, and the (S)-MDMA enantioisomers were determined. Several electrophoretic parameters, including the concentration of b-CD (aqueous, 25–60 mM; nonaqueous, 20–150 mM) used in the electrophoretic separation and the amount of organic solvents required for the separation, were optimized. Keywords: Aqueous and nonaqueous buffers; Capillary electrophoresis; Enantioseparation; 3,4- Methylenedioxymethamphetamine DOI 10.1002/elps.200410374 1 Introduction (2)-methamphetamine can also be extracted from a Vicks Inhaler [4] and that (2)-methamphetamine is used 3,4-Methylenedioxymethamphetamine (MDMA) was first in certain prescription drugs [5]. To avoid errors in judg- synthesized (1912) and patented (1914) by Merck Phar- ment, an enantiomeric analysis would be highly desir- maceuticals. The toxicity of MDMA was examined in able.
    [Show full text]
  • Asymmetric Synthesis of Α-N,N-Dialkylamino Alcohols by Transfer Hydrogenation of N,N-Dialkylamino Ketones
    Acta Poloniae Pharmaceutica ñ Drug Research, Vol. 67 No. 6 pp. 717ñ721, 2010 ISSN 0001-6837 Polish Pharmaceutical Society ASYMMETRIC SYNTHESIS OF α-N,N-DIALKYLAMINO ALCOHOLS BY TRANSFER HYDROGENATION OF N,N-DIALKYLAMINO KETONES TOMASZ KOSMALSKI Department of Organic Chemistry, Collegium Medicum, Nicolaus Copernicus University, M. Curie-Sk≥odowska 9, 85-067, Bydgoszcz, Poland Keywords: β-amino alcohols, Noyori`s catalyst, asymmetric transfer hydrogenation (ATH) β-Amino alcohols are important physiological- instrument. MS spectra were recorded on an AMD ly active compounds (1, 2a,b), also used as ligands 604 spectrometer. Optical rotations were measured (3, 4), and precursors of oxazaborolidines (5). on an Optical Activity PolAAr 3000 automatic Various methods for their asymmetric synthesis, polarimeter. GC analyses were performed on a such as the reduction of α-functionalized ketones Perkin-Elmer Auto System XL chromatograph, with hydrides (6, 7), catalytic hydrogenation of HPLC analyses were performed on a Shimadzu LC- amino ketones (8), reduction with borane/oxaza- 10 AT chromatograph. Melting points were deter- borolidines (9, 10), and other approaches (11ñ13) mined in open glass capillaries and are uncorrected. have been developed. However, the existing meth- Elemental analyses were performed by the ods are not ideal. For example, chiral β-chloro Microanalysis Laboratory, Institute of Organic hydrins, obtained by the reduction of α-chloro Chemistry, Polish Academy of Sciences, Warszawa. ketones, can be transformed into β-amino alcohols Silica gel 60, Merck 230ñ400 mesh was used for by treatment with secondary amines, however, mix- preparative column chromatography. Macherey- tures of isomers are sometimes formed (14). Nagel Polygram Sil G/UV254 0.2 nm plates were Asymmetric transfer hydrogenation (15, 16) used for analytical TLC.
    [Show full text]
  • Application of High Resolution Mass Spectrometry for the Screening and Confirmation of Novel Psychoactive Substances Joshua Zolton Seither [email protected]
    Florida International University FIU Digital Commons FIU Electronic Theses and Dissertations University Graduate School 4-25-2018 Application of High Resolution Mass Spectrometry for the Screening and Confirmation of Novel Psychoactive Substances Joshua Zolton Seither [email protected] DOI: 10.25148/etd.FIDC006565 Follow this and additional works at: https://digitalcommons.fiu.edu/etd Part of the Chemistry Commons Recommended Citation Seither, Joshua Zolton, "Application of High Resolution Mass Spectrometry for the Screening and Confirmation of Novel Psychoactive Substances" (2018). FIU Electronic Theses and Dissertations. 3823. https://digitalcommons.fiu.edu/etd/3823 This work is brought to you for free and open access by the University Graduate School at FIU Digital Commons. It has been accepted for inclusion in FIU Electronic Theses and Dissertations by an authorized administrator of FIU Digital Commons. For more information, please contact [email protected]. FLORIDA INTERNATIONAL UNIVERSITY Miami, Florida APPLICATION OF HIGH RESOLUTION MASS SPECTROMETRY FOR THE SCREENING AND CONFIRMATION OF NOVEL PSYCHOACTIVE SUBSTANCES A dissertation submitted in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY in CHEMISTRY by Joshua Zolton Seither 2018 To: Dean Michael R. Heithaus College of Arts, Sciences and Education This dissertation, written by Joshua Zolton Seither, and entitled Application of High- Resolution Mass Spectrometry for the Screening and Confirmation of Novel Psychoactive Substances, having been approved in respect to style and intellectual content, is referred to you for judgment. We have read this dissertation and recommend that it be approved. _______________________________________ Piero Gardinali _______________________________________ Bruce McCord _______________________________________ DeEtta Mills _______________________________________ Stanislaw Wnuk _______________________________________ Anthony DeCaprio, Major Professor Date of Defense: April 25, 2018 The dissertation of Joshua Zolton Seither is approved.
    [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]
  • (Ph OH N N Me O YO O YO
    US 20070265293A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2007/0265293 A1 Boyd et al. (43) Pub. Date: Nov. 15, 2007 (54) (S)-N-METHYLNALTREXONE Publication Classification (76) Inventors: Thomas A. Boyd, Grandview, NY (51) Int. Cl. (US); Howard Wagoner, Warwick, NY A6II 3L/4355 (2006.01) (US); Suketu P. Sanghvi, Kendall Park, A6M II/00 (2006.01) NJ (US); Christopher Verbicky, A6M I5/08 (2006.01) Broadalbin, NY (US); Stephen 39t. 35O C Andruski, Clifton Park, NY (US) (2006.01) A6IP 3L/00 (2006.01) Correspondence Address: St. 4. CR WOLF GREENFIELD & SACKS, P.C. (2006.01) 6OO ATLANTIC AVENUE 3G (i. 308: BOSTON, MA 02210-2206 (US) A6IP 33/02 (2006.01) C07D 489/00 (2006.01) (21) Appl. No.: 11/441,452 (52) U.S. Cl. .............. 514/282; 128/200.23; 128/202.17; (22) Filed: May 25, 2006 546/45 Related U.S. Application Data (57) ABSTRACT This invention relates to S-MNTX, methods of producing (60) Provisional application No. 60/684,570, filed on May S-MNTX, pharmaceutical preparations comprising 25, 2005. S-MNTX and methods for their use. O G M Br Br e (pH OH N N Me O YO O YO OH OH R-MNTX S-MNTX Patent Application Publication Nov. 15, 2007 Sheet 1 of 6 US 2007/0265293 A1 Fig. 1 OH OH Me-N Me-N D / O O -----BBr, O O CHCI NMP, 3 AUTOCLAVE, 70'C OMe OH 1 2 Br OH As GE) G As 69 GOH Me-N ION Me-N -lass O SO EXCHANGE O SO OH OH 3 S-MNTX 1 - OXYCODONE 2 - OXYMORPHONE 3 - ODIDE SALT OF S-MNTX Fig.
    [Show full text]