DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. No.: US 2014/0212486A1 LEDERMAN Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) Patent Application Publication (10) Pub. No.: US 2014/0212486A1 LEDERMAN Et Al US 20140212486A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0212486A1 LEDERMAN et al. (43) Pub. Date: Jul. 31, 2014 (54) ISOMETHEPTENE ISOMER (52) U.S. Cl. CPC ............. C07C 211/21 (2013.01); C07C 59/285 (71) Applicant: TONIX PHARMACEUTICALS INC., (2013.01); A61 K3I/I31 (2013.01); A61 K NEW YORK, NY (US) 45/06 (2013.01); C07C 209/68 (2013.01); C07B 53/00 (2013.01); A61 K3I/I67 (72) Inventors: SETH LEDERMAN, NEW YORK, NY (2013.01); A61 K31/192 (2013.01); A61 K (US); BRUCE DAUGHERTY, 3 1/522 (2013.01); A61 K31/4152 (2013.01) MENDHAM, NJ (US); LELAND J. USPC ........... 424/463:564/509;562/582: 514/671; GERSHELL NEW YORK, NY (US); 424/464: 514/263.34: 514/.404 DARRYL RIDEOUT, PARKTON, MD (57) ABSTRACT DIEGO,(US); ANDREW CA (US) KAWASAKI, SAN The invention relates to a purified Isometheptene compound comprising the structure according to Formula (I), (73) Assignee: TONIX PHARMACEUTICALS INC., NEW YORK, NY (US) (6-methylamino-2-methylheptene) (21)21) AppAppl. No.: 14/158,7359 21 NH (22) Filed: Jan. 17, 2014 Related U.S. Application Data or a hydrochloride, or a pharmaceutically acceptable addition (60) Provisional application No. 61/926,739, filed on Jan. salt thereof. In particular, the disclosure relates to the synthe 13, 2014, provisional application No. 61/814,664, sis, purification and characterization of an Isometheptene filed on Apr. 22, 2013, provisional application No. isomer mucate crystal 2, wherein the Isometheptene isomer 2 61/793.456, filed on Mar. 15, 2013, provisional appli- is stereochemically characterized as (R)-enantiomer, respec cation No. 61/754,281, filed on Jan. 18, 2013. tively. The Isometheptene (R)-enantiomeractivity indicates a selective centrally acting selective ligand for Imidazoline Publication Classification Subtype 1 (I.1) receptor sites; and more specifically, the dis closure provides an antihypertensive composition for treat (51) Int. Cl. ment of migraine and other neurovascular or neurogenic pain CD7C 2 II/2 (2006.01) from abdominal distress. (R)-Isometheptene enantiomer or A6 IK3I/3 (2006.01) isomer 2 may be an anti-hypertensive agent with lower side A6 IK 45/06 (2006.01) effects than the racemate form. Therefore (R)-Isometheptene A6 IK3 L/452 (2006.01) is believed to be effective against episodic tension-type head C07B 53/00 (2006.01) aches (ETTH). The (R)-Isometheptene enantiomer or isomer A6 IK3I/67 (2006.01) 2 is believed to effectively lower blood pressure, used alone or A6 IK3I/92 (2006.01) together with other headache ameliorating drugs. Methods of A6 IK3I/522 (2006.01) synthesis and treatment are described. Regarding (R)- C07C 59/285 (2006.01) Isometheptene crystals data of X-ray crystallography are pre CD7C 209/68 (2006.01) sented. C23 Patent Application Publication Jul. 31, 2014 Sheet 1 of 24 US 2014/021248.6 A1 HPLC SOMER 2 ELS1A, Signal Voltage (MAR-2011-067WR111007491.D) s 7OO 6OO 500 400 300 200 1OO O O 5 1O 15 2O min FIG. 1 Patent Application Publication Jul. 31, 2014 Sheet 2 of 24 US 2014/021248.6 A1 HPLC BLANK ELS1A, Signal Voltage (MAR-2011-067WCN(1603)BLK.D) mV 16OO 1400 1200 1 OOO 800 600 400 200 O 5 10 15 2O min FIG.2 Patent Application Publication Jul. 31, 2014 Sheet 3 of 24 US 2014/021248.6 A1 Retention Time 300 300 200 200 o CC E 1OO 100 O O O 5 10 15 20 25 30 35 40 45 Minutes CHIRAL HPLC ISOMER 2 FIG. 3 Patent Application Publication Jul. 31, 2014 Sheet 4 of 24 US 2014/021248.6 A1 CHIRAL HPLC RACEMIC SOMRTHPTENE 2000. Retention Time 2000 1500 1500 D 1000 1000 E 500 500 O --0 O 5 10 15 20 25 30 35 40 45 Minutes FIG. 4 Patent Application Publication Jul. 31, 2014 Sheet 5 of 24 US 2014/021248.6 A1 LC OF SOMER 2 *Maximum Chromatogram of DADATAMAR-11WR111007491B.D, Signalld A mAU 500 400 300 200 100 O 1 2 3 4 5 6 min Patent Application Publication Jul. 31, 2014 Sheet 6 of 24 US 2014/0212486A1 ZNJEWNOSIHWNHI Patent Application Publication Jul. 31, 2014 Sheet 7 of 24 US 2014/021248.6 A1 MASS SPECTRUM OF SOMER 2 Intens. x107 1 go--- 6 Time (min) AR11 1007491B.D.: TIC AIIMS Intens.x107 +MS, 1.9min #78 1.O 0.8 O.6 0.4 0.2 O.O 125 150 175 200 225 250 250 300 m/z. FIG. 7 Patent Application Publication Jul. 31, 2014 Sheet 8 of 24 US 2014/021248.6 A1 HPLC OF SOMER 1 ELS1A, Signal Voltage (MAR-2011-08OWR111007807-1.D) O 5 10 15 2O min FIG. 8 Patent Application Publication Jul. 31, 2014 Sheet 9 of 24 US 2014/021248.6 A1 HPLC BLANK ISOMER 1 ELS1A, Signal Voltage (MAR-2011-08070N(1803)BLKD) mV 700 600 5OO 400 300 200 1 OO O 5 10 15 2O min F.G. 9 Patent Application Publication Jul. 31, 2014 Sheet 11 of 24 US 2014/021248.6 A1 CHRAL HPLC SOMER 1 800 800 Retention Time 600 600 400 400 CC E 200 200 O O O 5 1O 15 20 25 30 35 40 45 Minutes FIG 11 Patent Application Publication Jul. 31, 2014 Sheet 12 of 24 US 2014/021248.6 A1 CHRAL HPLC OF RACEMIC SOMETHEPTENE Retention Time 800 800 6OO 600 400 400 200 Patent Application Publication Jul. 31, 2014 Sheet 13 of 24 US 2014/021248.6 A1 Patent Application Publication Jul. 31, 2014 Sheet 14 of 24 US 2014/021248.6 A1 H NMR of (R)-isometheptene (R)-Mosher amide There is no (S)peak at 4.84 ppm. CO) i? coco w OONO)o N. cow v. N. N. row rCNCNOOCOcy) was Ol?on CNV cocV wo Ocn w v. C. Cdo odoo cycNw-doon cold Vool w crocnwoodoococoncNwe doo odd c2c2 v V v v CoccoccNNNNNN rint (Occoncy Yooooooooooooo LLO LOOLOLLOOOOLOLOLOr riv rif r rve r rrr rrrrrr cycrococcydcoccy) cyco 1300FOCU.808A 7-57-Crude CDC13, H-1 NUMEGA 2-19-2013 s ce 5. 5.8 5.7 5.6 5.5 5.4 5.3 5.2 5. 5.0 5.7 48 4.7 4.6 4.5 44 4.3 4.2 4.1 40 3.9 3.8 f1 (ppm) FIG. 14 Patent Application Publication Jul. 31, 2014 Sheet 15 of 24 US 2014/021248.6 A1 H NMR mixture of (R)- and (S)-isometheptene (R)-Mosheramide. nn door CNorward ld onw Cococoon rinivas we coco won Now WO w Cd on N.N. cocococo v - V - oooooooooon cocow rary sco canno?coso o NNNNNNNNNNN sus Losursrinus LSLs LSLs Louilors rrrrrrrrrrrrri. SSS-yl)-2sld-- ' ' ' ----iss N2-12s--- 1206FOCU,119B 7-14-lSomer 2 CDC13, H-1 NUMEGA 11-15-12 (S) (R) H - I - st st se s 75 7.0 6.5 6.0 5.5 5.0 4.5 f1 (ppm) Patent Application Publication Jul. 31, 2014 Sheet 16 of 24 US 2014/021248.6 A1 ::::::iii. 335i Patent Application Publication Jul. 31, 2014 Sheet 17 of 24 US 2014/021248.6 A1 Patent Application Publication Jul. 31, 2014 Sheet 18 of 24 US 2014/021248.6 A1 Patent Application Publication Jul. 31, 2014 Sheet 19 of 24 US 2014/021248.6 A1 Patent Application Publication Jul. 31, 2014 Sheet 20 of 24 US 2014/021248.6 A1 *** Patent Application Publication Jul. 31, 2014 Sheet 21 of 24 US 2014/021248.6 A1 Binding of Isometheptene to i-Imidazoline receptor 1OO o (S)-isometheptene Mucate, Ki= 1100 nM o (R)-isomethepene Mucate, Kil 18nM v isometheptene Mucate USP, Ki= 42nM 80 Log Compound), M FIG 21 Patent Application Publication Jul. 31, 2014 Sheet 22 of 24 US 2014/021248.6 A1 Binding of isometheptene to 2-Imidazoline receptor o (S)-isometheptene Mucate, K=180 nM o (R)-isomethepene Mucate, Ki-62 nM v isometheptene Mucate USP, Ki= 93 nM 8 O 6 O Log Compound), M FG, 22 Patent Application Publication Jul. 31, 2014 Sheet 24 of 24 US 2014/021248.6 A1 110 100 90 80 70 60 50 40 30 20 10 O m -11 - 10 -9 -8 -7 -6 -5 -4 -3 -2 log drug M lodo-clonidine 104 V Amino-clonidine 227 O Guanabenz 1,410 O 2-BF 25,740 O ldaZOXan 71,070 F.G. 24 US 2014/021248.6 A1 Jul. 31, 2014 SOMETHEPTENESOMER ergotamines in the treatment of vascular headaches. Clin. Med. 1970. 77:33-36; Yuill, G. M., et al. A double-blind 0001. This patent application claims priority from Provi crossover trial of Isometheptene mucate compound and sional patent applications 61/926,739 filed Jan. 13, 2014: ergotamine in migraine. Br J Clin Pract. 1972 26(2):76-9. 61/814,664 filed Apr. 22, 2013: 61/793.456 filed Mar. 15, PMID:4552744: Diamond, S. Treatment of migraine with 2013; and 61/754,281 filed Jan. 18, 2013; which prior disclo Isometheptene, acetaminophen, and dichloralphenaZone Sures are incorporated in the present application. combination: A double-blind, crossover trial. Headache. 0002 All references cited in this specification, and their 1976 15(4):282-7. PMID: 1107267: Valdivia, L. F. Pharmaco references, are incorporated by reference herein in their logical analysis of the mechanisms involved in the tachy entirety where appropriate for teachings of additional or alter cardic and vasopressor responses to the antimigraine agent, native details, features, and/or technical background. Isometheptene, in pithed rats. Life Sciences 2004. 74:3223 3234; Freitag, F G. Comparative Study of a Combination of FIELD OF THE INVENTION Isometheptene Mucate, Dichloralphenazone With Acetami 0003.
Load more

Recommended publications
  • Educational Commentary – Testing for Amphetamines and Related Compounds
    EDUCATIONAL COMMENTARY – TESTING FOR AMPHETAMINES AND RELATED COMPOUNDS Learning Outcomes Upon completion of this exercise, participants will be able to: • list amphetamine-like compounds that may be detected by immunoassay screening tests for amphetamines. • describe the 3 types of amphetamine immunoassays based on their antibody specificity. • discuss common causes of false-positive results when testing for amphetamines. Correct interpretation of testing results for amphetamines and related compounds is dependent on many factors including an understanding of the nomenclature, structure, and metabolism of these compounds. The class of phenethylamine compounds having varying degrees of sympathomimetic activity include amphetamine, methamphetamine, and many other compounds known by several names including amphetamines (as a group), designer drugs often grouped together as ecstasy [3,4- methylenedioxymethamphetamine (MDMA); 3,4-methylenedioxyamphetamine (MDA), and 3,4- methylenedioxy-N-ethylamphetamine (MDEA)], and sympathomimetic amines including ephedrine, pseudoephedrine, and phenylpropanolamine found in over-the-counter (OTC) medications. Amphetamine, a primary amine, and methamphetamine, a secondary amine, have a stereogenic center and have enantiomers or optical isomers designated d (or +) for dextrorotatory and l (or -) for levorotatory. In general, the d isomers are the more physiologically active compounds, but pharmaceutical preparations may consist of either isomer or a mixture of both isomers. When the mixture contains equal concentrations of the 2 enantiomers, it is known as a racemic mixture. The existence of enantiomers for amphetamines creates analytical and interpretative problems. Immunoassay Screening The primary screening methods for detecting amphetamines are immunoassays. The structural similarity to amphetamine or methamphetamine of the compounds previously mentioned makes it difficult to produce antibodies specific for amphetamine, methamphetamine, or both.
    [Show full text]
  • Drug Formulary Medi-Cal/Healthy Families Drug Formulary • 2014
    2014 Drug Formulary Medi-Cal/Healthy Families Drug Formulary • 2014 Medi-Cal/Healthy Families Drug Formulary • 2014 TABLE OF CONTENTS MOLINA HEALTHCARE MEDI-CAL/HEALTHY FAMILIES DRUG FORMULARY ....................................................................................4 PRESCRIPTION CLAIMS PROCESSOR .........................................................5 USING THE MOLINA MEDI-CAL/HEALTHY FAMILIES DRUG FORMULARY ....................................................................................6 CLINICAL CONSIDERATIONS .........................................................................6 INDIVIDUAL PRESCRIPTIONS ........................................................................6 GENERIC MEDICATIONS .................................................................................7 PRIOR AUTHORIZATION REQUEST PROCEDURE ......................................7 STEP THERAPY PROCEDURE .......................................................................7 PRESCRIPTION QUANTITY .............................................................................7 URGENT AND AFTER-HOURS MEDICATION POLICY ..................................8 TELEPHONE PRESCRIPTIONS.......................................................................8 DRUG FORMULARY .........................................................................................9 Chapter 1 ANALGESICS ..............................................................................9 Chapter 2 ANTIDIABETIC AGENTS ..........................................................12 Chapter
    [Show full text]
  • Customs Tariff - Schedule
    CUSTOMS TARIFF - SCHEDULE 99 - i Chapter 99 SPECIAL CLASSIFICATION PROVISIONS - COMMERCIAL Notes. 1. The provisions of this Chapter are not subject to the rule of specificity in General Interpretative Rule 3 (a). 2. Goods which may be classified under the provisions of Chapter 99, if also eligible for classification under the provisions of Chapter 98, shall be classified in Chapter 98. 3. Goods may be classified under a tariff item in this Chapter and be entitled to the Most-Favoured-Nation Tariff or a preferential tariff rate of customs duty under this Chapter that applies to those goods according to the tariff treatment applicable to their country of origin only after classification under a tariff item in Chapters 1 to 97 has been determined and the conditions of any Chapter 99 provision and any applicable regulations or orders in relation thereto have been met. 4. The words and expressions used in this Chapter have the same meaning as in Chapters 1 to 97. Issued January 1, 2020 99 - 1 CUSTOMS TARIFF - SCHEDULE Tariff Unit of MFN Applicable SS Description of Goods Item Meas. Tariff Preferential Tariffs 9901.00.00 Articles and materials for use in the manufacture or repair of the Free CCCT, LDCT, GPT, UST, following to be employed in commercial fishing or the commercial MT, MUST, CIAT, CT, harvesting of marine plants: CRT, IT, NT, SLT, PT, COLT, JT, PAT, HNT, Artificial bait; KRT, CEUT, UAT, CPTPT: Free Carapace measures; Cordage, fishing lines (including marlines), rope and twine, of a circumference not exceeding 38 mm; Devices for keeping nets open; Fish hooks; Fishing nets and netting; Jiggers; Line floats; Lobster traps; Lures; Marker buoys of any material excluding wood; Net floats; Scallop drag nets; Spat collectors and collector holders; Swivels.
    [Show full text]
  • Review Memorandum
    510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k062575 B. Purpose for Submission: New device C. Measurand: Amphetamine, Barbiturates, Benzodiazepines, Cocaine, Methamphetamine, Phencyclidine, Methadone, Opiates, THC, and Tricyclic Antidepressants. D. Type of Test: Qualitative immunoassay E. Applicant: Princeton BioMeditech Corporation F. Proprietary and Established Names: AccuSign RC DOA10 (MET/OPI/COC/THC/PCP/BZO/BAR/MTD/TCA/AMP) StatusFirst DOA10 (MET/OPI/COC/THC/PCP/BZO/BAR/MTD/TCA/AMP) G. Regulatory Information: Product Code Classification Regulation Section Panel LAG II 862.3610 91 (Tox) Methamphetamine test system DJG II 862.3650, Enzyme 91 (Tox) Immunoassay, Opiates DIO II 862.3250, Enzyme 91 (Tox) Immunoassay, Cocaine and Cocaine Metabolites 1 Product Code Classification Regulation Section Panel DKE II 862.3870 91 (Tox) Cannabinoid test system LCM Unclassified (510k 862.3100 Enzyme 91 (Tox) required) immunoassay, Phencyclidine DKZ II 862.3100 91 (Tox) Amphetamine test system JXM II 862.3170 Enzyme 91 (Tox) immunoassay, Barbiturate DIS II 862.3150 91 (Tox) Barbiturate test system DJR II 862.3620 91 (Tox) Methadone test system LFI II 862.3910 Tricyclic 91 (Tox) antidepressant drugs test system H. Intended Use: 1. Intended use(s): See indications for use below. 2. Indication(s) for use: Immunoassay for the qualitative detection of methamphetamine, opiates, cocaine metabolite, THC metabolite, phencyclidine, benzodiazepines, barbiturates, tricyclic antidepressants, methadone, and amphetamine in human urine to assist in screening of drug of abuse samples. The detecting cut-off concentrations are as follows: MET D-Methamphetamine 1000 ng/mL OPI Morphine 300 ng/mL COC Benzoylecgonine 300 ng/mL THC 11-nor-Δ9-9-carboxylic acid 50 ng/mL PCP Phencyclidine 25 ng/mL Benzodiazepine Oxazepam 300 ng/mL Barbiturate Secobarbital 300 ng/mL Methadone Methadone 300 ng/mL TCA Nortriptyline 1000 ng/mL AMP D-Amphetamine 1000 ng/mL 2 This assay provides only a preliminary analytical test result.
    [Show full text]
  • Acetaminophen, Isometheptene, and Dichloralphenazone
    PATIENT & CAREGIVER EDUCATION Acetaminophen, Isometheptene, and Dichloralphenazone This information from Lexicomp® explains what you need to know about this medication, including what it’s used for, how to take it, its side effects, and when to call your healthcare provider. Brand Names: US Nodolor [DSC] Warning This drug has acetaminophen in it. Liver problems have happened with the use of acetaminophen. Sometimes, this has led to a liver transplant or death. Most of the time, liver problems happened in people taking more than 4,000 mg (milligrams) of acetaminophen in a day. People were also often taking more than 1 drug that had acetaminophen. Avoid drinking alcohol while taking this drug. What is this drug used for? It is used to treat headaches. Acetaminophen, Isometheptene, and Dichloralphenazone 1/8 What do I need to tell my doctor BEFORE I take this drug? If you have an allergy to acetaminophen, isometheptene, dichloralphenazone, or any other part of this drug. If you are allergic to this drug; any part of this drug; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had. If you have any of these health problems: Glaucoma, heart disease, high blood pressure, liver disease, or poor kidney function. If you have blood vessel problems, including in the heart or brain. If you have had a recent heart attack or stroke. If you have taken certain drugs for depression or Parkinson’s disease in the last 14 days. This includes isocarboxazid, phenelzine, tranylcypromine, selegiline, or rasagiline. Very high blood pressure may happen.
    [Show full text]
  • Title 16. Crimes and Offenses Chapter 13. Controlled Substances Article 1
    TITLE 16. CRIMES AND OFFENSES CHAPTER 13. CONTROLLED SUBSTANCES ARTICLE 1. GENERAL PROVISIONS § 16-13-1. Drug related objects (a) As used in this Code section, the term: (1) "Controlled substance" shall have the same meaning as defined in Article 2 of this chapter, relating to controlled substances. For the purposes of this Code section, the term "controlled substance" shall include marijuana as defined by paragraph (16) of Code Section 16-13-21. (2) "Dangerous drug" shall have the same meaning as defined in Article 3 of this chapter, relating to dangerous drugs. (3) "Drug related object" means any machine, instrument, tool, equipment, contrivance, or device which an average person would reasonably conclude is intended to be used for one or more of the following purposes: (A) To introduce into the human body any dangerous drug or controlled substance under circumstances in violation of the laws of this state; (B) To enhance the effect on the human body of any dangerous drug or controlled substance under circumstances in violation of the laws of this state; (C) To conceal any quantity of any dangerous drug or controlled substance under circumstances in violation of the laws of this state; or (D) To test the strength, effectiveness, or purity of any dangerous drug or controlled substance under circumstances in violation of the laws of this state. (4) "Knowingly" means having general knowledge that a machine, instrument, tool, item of equipment, contrivance, or device is a drug related object or having reasonable grounds to believe that any such object is or may, to an average person, appear to be a drug related object.
    [Show full text]
  • PQA Measure Specifications ______
    PQA Measure Specifications ______________________________________________________________________________ Table DDI-A: Target Medications and Precipitant Medications Table DDI-A Category Target Drug or Drug Class (Step 1) Precipitant Drug or Drug Class (Step 2) A Benzodiazepines: alprazolam, midazolam, triazolam Azole antifungal agents: ketoconazole, itraconazole, fluconazole, posaconazole, voriconazole B carbamazepine Clarithromycin, erythromycin, telithromycin C cyclosporine Rifamycins: rifampin, rifabutin, rifapentine D digoxin clarithromycin, erythromycin, azithromycin, telithromycin E Ergot alkaloids: ergotamine, dihydroergotamine clarithromycin, erythromycin, telithromycin F Estrogen/progestin oral contraceptives: Rifamycins: rifampin, rifabutin, rifapentine desogestrel-ethinyl estradiol, drospirenone-ethinyl estradiol, estradiol valerate-dienogest, ethinyl estradiol-ethynodiol, ethinyl estradiol-levonorgestrel, ethinyl estradiol-norethindrone, ethinyl estradiol- norgestimate, ethinyl estradiol-norgestrel, mestranol- norethindrone G MAO Inhibitors: isocarboxazid, linezolid, phenelzine, Sympathomimetics: amphetamines, atomoxetine, rasagiline, selegiline, tranylcypromine, sibutramine benzphetamine, dextroamphetamine, diethylpropion, isometheptene, methamphetamine, methylphenidate, phendimetrazine, phentermine, phenylephrine, pseudoephedrine, tapentadol, dexmethylphenidate, lisdexamfetamine Serotonergic Agents: buspirone, citalopram, cyclobenzaprine, desvenlafaxine, dextromethorphan, duloxetine, escitalopram, fluoxetine, fluvoxamine,
    [Show full text]
  • Urine Drug Testing Methods3-5 Urine Drug Testing Specimen Validity3-4
    Urine Drug Testing Methods3-5 Type of Test Logistics Pearls • Inexpensive • High sensitivity, low specificity (higher potential for false positives) Initial Screening Test: • Fast • Opiate screen not sensitive for semisynthetic (e.g. oxycodone) or Immunoassay • Widely available synthetic opioids (e.g. fentanyl) Confirmatory Test: Gas chromatography-mass • High sensitivity, high specificity • Expensive spectrometry (GCMS)+ or • Expensive • Time consuming Liquid chromatography-mass • Detects medication even if concentration is low spectrometry (LCMS) + GCMS is considered the criterion standard for confirmatory testing; Immunoassay tests have high predictive values for marijuana and cocaine, but lower predictive values for opiates and amphetamines Urine Drug Testing Specimen Validity3-4 Normal Characteristics of a Urine Sample3-5 • Urine samples that are adulterated, substituted, or diluted may Temperature within 4 minutes of voiding: 90-100⁰F avoid detection of drug use4 pH: 4.5-8.0 • Urine collected in the early morning is most concentrated and Creatinine: > 20 mg/dL most reliable Specific gravity: > 1.003 • Excessive water intake and diuretic use can lead to diluted urine Nitrates: < 500 mcg/dL samples (Creatinine < 20) 3-4 • THC assays are sensitive to adulterants (e.g. Visine eyedrops) Volume: ≥ 30 mL 4 Source: https://www.healthquality.va.gov/guidelines/Pain/cot/VADoDOTCPGProviderSummary022817.pdf Urine Drug Testing (UDT) Federal Work Place Cut Off Values3-9 Initial Drug Test Level Confirmatory Drug Test Detection Period After Confirmatory
    [Show full text]
  • Appendix-2Final.Pdf 663.7 KB
    North West ‘Through the Gate Substance Misuse Services’ Drug Testing Project Appendix 2 – Analytical methodologies Overview Urine samples were analysed using three methodologies. The first methodology (General Screen) was designed to cover a wide range of analytes (drugs) and was used for all analytes other than the synthetic cannabinoid receptor agonists (SCRAs). The analyte coverage included a broad range of commonly prescribed drugs including over the counter medications, commonly misused drugs and metabolites of many of the compounds too. This approach provided a very powerful drug screening tool to investigate drug use/misuse before and whilst in prison. The second methodology (SCRA Screen) was specifically designed for SCRAs and targets only those compounds. This was a very sensitive methodology with a method capability of sub 100pg/ml for over 600 SCRAs and their metabolites. Both methodologies utilised full scan high resolution accurate mass LCMS technologies that allowed a non-targeted approach to data acquisition and the ability to retrospectively review data. The non-targeted approach to data acquisition effectively means that the analyte coverage of the data acquisition was unlimited. The only limiting factors were related to the chemical nature of the analyte being looked for. The analyte must extract in the sample preparation process; it must chromatograph and it must ionise under the conditions used by the mass spectrometer interface. The final limiting factor was presence in the data processing database. The subsequent study of negative MDT samples across the North West and London and the South East used a GCMS methodology for anabolic steroids in addition to the General and SCRA screens.
    [Show full text]
  • Drug and Medication Classification Schedule
    KENTUCKY HORSE RACING COMMISSION UNIFORM DRUG, MEDICATION, AND SUBSTANCE CLASSIFICATION SCHEDULE KHRC 8-020-1 (11/2018) Class A drugs, medications, and substances are those (1) that have the highest potential to influence performance in the equine athlete, regardless of their approval by the United States Food and Drug Administration, or (2) that lack approval by the United States Food and Drug Administration but have pharmacologic effects similar to certain Class B drugs, medications, or substances that are approved by the United States Food and Drug Administration. Acecarbromal Bolasterone Cimaterol Divalproex Fluanisone Acetophenazine Boldione Citalopram Dixyrazine Fludiazepam Adinazolam Brimondine Cllibucaine Donepezil Flunitrazepam Alcuronium Bromazepam Clobazam Dopamine Fluopromazine Alfentanil Bromfenac Clocapramine Doxacurium Fluoresone Almotriptan Bromisovalum Clomethiazole Doxapram Fluoxetine Alphaprodine Bromocriptine Clomipramine Doxazosin Flupenthixol Alpidem Bromperidol Clonazepam Doxefazepam Flupirtine Alprazolam Brotizolam Clorazepate Doxepin Flurazepam Alprenolol Bufexamac Clormecaine Droperidol Fluspirilene Althesin Bupivacaine Clostebol Duloxetine Flutoprazepam Aminorex Buprenorphine Clothiapine Eletriptan Fluvoxamine Amisulpride Buspirone Clotiazepam Enalapril Formebolone Amitriptyline Bupropion Cloxazolam Enciprazine Fosinopril Amobarbital Butabartital Clozapine Endorphins Furzabol Amoxapine Butacaine Cobratoxin Enkephalins Galantamine Amperozide Butalbital Cocaine Ephedrine Gallamine Amphetamine Butanilicaine Codeine
    [Show full text]
  • No 1223/2009 of the EUROPEAN PARLIAMENT and of the COUNCIL of 30 November 2009 on Cosmetic Products (Recast) (Text with EEA Relevance) (OJ L 342, 22.12.2009, P
    02009R1223 — EN — 03.12.2020 — 025.001 — 1 This text is meant purely as a documentation tool and has no legal effect. The Union's institutions do not assume any liability for its contents. The authentic versions of the relevant acts, including their preambles, are those published in the Official Journal of the European Union and available in EUR-Lex. Those official texts are directly accessible through the links embedded in this document ►B REGULATION (EC) No 1223/2009 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 30 November 2009 on cosmetic products (recast) (Text with EEA relevance) (OJ L 342, 22.12.2009, p. 59) Amended by: Official Journal No page date ►M1 Commission Regulation (EU) No 344/2013 of 4 April 2013 L 114 1 25.4.2013 ►M2 Commission Regulation (EU) No 483/2013 of 24 May 2013 L 139 8 25.5.2013 ►M3 Commission Regulation (EU) No 658/2013 of 10 July 2013 L 190 38 11.7.2013 ►M4 Commission Regulation (EU) No 1197/2013 of 25 November 2013 L 315 34 26.11.2013 ►M5 Commission Regulation (EU) No 358/2014 of 9 April 2014 L 107 5 10.4.2014 ►M6 Commission Regulation (EU) No 866/2014 of 8 August 2014 L 238 3 9.8.2014 ►M7 Commission Regulation (EU) No 1003/2014 of 18 September 2014 L 282 1 26.9.2014 ►M8 Commission Regulation (EU) No 1004/2014 of 18 September 2014 L 282 5 26.9.2014 ►M9 Commission Regulation (EU) 2015/1190 of 20 July 2015 L 193 115 21.7.2015 ►M10 Commission Regulation (EU) 2015/1298 of 28 July 2015 L 199 22 29.7.2015 ►M11 Commission Regulation (EU) 2016/314 of 4 March 2016 L 60 59 5.3.2016 ►M12 Commission Regulation (EU)
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]