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Prescription & Illicit Drug Certified Reference Materials Many analgesics clinically prescribed to manage chronic pain carry warranted concerns over safety and abuse liability. Further complications can arise from drug-drug interactions when stimulants or other illicit compounds are also abused. Cayman Chemical offers Certified Reference Materials (CRMs) to help identify, confirm, and quantify many of the major opioids, benzodiazepines, psychoactive drugs, and other controlled substances. Our CRMs meet ISO/IEC 17025 and ISO 17034 standards and are sold as quantitative solutions in sealed ampules. Opioid CRMs Benzodiazepine CRMs Item No. Product Name Item No. Product Name ISO60128 Acetyl fentanyl (hydrochloride) (CRM) ISO60185 Alprazolam (CRM) 23060 Acrylfentanyl (hydrochloride) (CRM) ISO60181 Clonazepam (CRM) 25936 Benzyl fentanyl (hydrochloride) (CRM) 25614 Clonazolam (CRM) ISO60178 Buprenorphine (hydrochloride) (CRM) ISO60177 Diazepam (CRM) 19734 Butyryl fentanyl (hydrochloride) (CRM) 28623 Diclazepam (CRM) 19884 Carfentanil (CRM) 20991 Etizolam (CRM) 26637 Crotonyl fentanyl (CRM) 25577 Flualprazolam (CRM) 23603 Cyclopropyl fentanyl (hydrochloride) (CRM) 26352 Flubromazolam (CRM) ISO60197 Fentanyl (hydrochloride) (CRM) 18160 Flurazepam (CRM) 25615 β-methyl Fentanyl (hydrochloride) (CRM) 19391 Midazolam (CRM) 19795 FIBF (hydrochloride) (CRM) 19206 Nimetazepam (CRM) 19826 para-Fluorobutyryl fentanyl (hydrochloride) (CRM) ISO60172 Phenazepam (CRM) 19633 Furanyl fentanyl (hydrochloride) (CRM) ISO60182 Temazepam (CRM) ISO60187 Heroin (CRM) Common benzodiazepines listed, more benzodiazepines and their metabolites and internal standards available online 23540 Methoxyacetyl fentanyl (hydrochloride) (CRM) 18567 Mitragynine (CRM) Request a physical copy of the 19635 Ocfentanil (hydrochloride) (CRM) Benzodiazepine Metabolism 25887 Phenyl fentanyl (hydrochloride) (CRM) 22429 Remifentanil (hydrochloride) (CRM) Wall Poster for your lab! 18660 Tapentadol (hydrochloride) (CRM) BENZODIAZEPINE METABOLISM LAB GUIDE 7-Halogenated-1,4-Benzodiazepines 7-Nitro-1,4-Benzodiazepines Half-Life of Common Benzodiazepines H H O O H O O O Drug (Brand Name) Half-Life (h)+Half-LifePrimary (hr) Metabolite+ (half-life, h)+ N N N N N O O Long Half-Life (effective >24 h)hr) 19397 U-47700 (CRM) OH OH OH R N B O2N N H2N N N N N N Diazepam (Valium) 20-100 20-100Nordiazepam (36-200) A H H R' R CE R R B R Chlordiazepoxide (Librium) (Librium) 5-30 5-30Nordiazepam (36-200) H 1 O O Clorazepate (Tranxene) * * Nordiazepam (36-200) N N Biotransformation Pathway Prazepam (Centrax) * * Nordiazepam (36-200) OH 7 4 R N R N B H H Flurazepam (Dalmane) * * Desalkylflurazepam (40-250) R' R' Intermediate to Short Half-Life (effective 5-24 h)hr) H H Drug O O 1 O O O Nitrazepam (Alodorm) 15-38 15-387-Aminonitrazepam N N N N N OH Flunitrazepam (Rohypnol) 20-30 20-307-Aminoflunitrazepam B O N N O N 7 N 4 H N N H N N R N A 2 2 2 2 Temazepam (Restoril) 8-22 8-22Oxazepam (4-15) 25522 U-48800 (hydrochloride) (CRM) R' R A R CE R B R Bromazepam (Lectopam) 10-20 10-203-hydroxy Bromazepam Lorazepam (Ativan) 10-20 10-20Lorazepam Glucuronide H CH CO H CO R NO Drug Primary Metabolite 3 2 2 2 Alprazolam (Xanax) 6-20 6-20α-hydroxy Alprazolam Examples CE B Oxazepam (Serax) 4-15 4-15Oxazepam Glucuronide O O O H O Etizolam (Etizest) 3.4-7.1 3.4-7.1α-hydroxy Etizolam A B C D E N N N N Examples H Ultra-Short Half-Life (effective <5 h)hr) Cl N Cl N Cl N Br N O H O H O O O N N N N N Midazolam (Versed) <5 <5α-hydroxy Midazolam Cl F Cl OH O2N N O2N N O2N N Triazolam (Halcion) <5 <5α-hydroxy Triazolam N N Phase I Metabolite Diazepam* Diclazepam Fludiazepam Phenazepam H2N O2N F Cl + H O H O H O O R R Approximate half-life data adapted from Greenblatt, D.J., Shader, R.I., Divoll, M., et al. Br. J. Clin. Pharmacol. N N N N Flunitrazepam Nitrazepam Clonazepam 11 (Suppl 1), 11S-16S (1981) and Manchester, K.R., Lomas, E.C., Waters, L., et al. Drug Test Anal. 10(1), 37-53 (2018). OH OH OH *Indicates prodrugs or drug precursors that do not reach the systemic circulation in clinically important amounts. Cl N Cl N Cl N Cl N 23999 U-49900 (CRM) Cl Nordiazepam Lorazepam Oxazepam Temazepam OH H H CO2H NH2 *The primary metabolite of diazepam is nordiazepam Triazolobenzodiazepines Benzodiazepine Prodrugs via phase I demethylation. N N N H O H O H O F G H HO N N N N N N N N N CO2Et CO2H H H H H A A OH Cl N D Cl N CE Cl N R N R N R N Phase II Metabolite F F F Thienodiazepines R' R' R' Ethyl Loflazepate Loflazepate Desalkylflurazepam 24264 U-51754 (hydrochloride) (CRM) N N N HO N N N S N S N HO S N H Examples H O O H O N N N N N N O NH CO2H H N N N N OH H H OH H3C R A R A R N N N N O O N N N N Cl N Cl N Cl N Cl N Cl N O N N Br N HO2C OH 2 CE A OH Cl Cl F Clorazepate Nordiazepam Oxazepam Examples Alprazolam Triazolam Clonazolam Flubromazolam N N N O N N N 8-Nitrotriazolobenzodiazepines can also undergo Hydroxylation Reduction N N N N A E S S S S 19798 Valeryl fentanyl (hydrochloride) (CRM) (MW plus 16) (MW minus 30) Cl Br reduction to 8-aminotriazolobenzodiazepines. O N N N N N Dealkylation What is a Prodrug? Demethylation Sulfation Cl Cl F Cl B F Cl N A prodrug is a drug substance that needs to be (MW minus 14) (MW plus 80) Clotiazepam Etizolam Fluclotizolam Brotizolam converted into the pharmacologically active agent Decarboxylation Glucuronidation View a complete list of parent compounds, metabolites, by metabolic or physiochemical transformation.1 C G Thienodiazepines contain a thiophene ring in place of the (MW minus 44) (MW plus 176) and labeled standards at www.caymanchem.com 1. Drago, D., Pacifici, E., and Bain, S. Chapter 3 Drugs. An overview of FDA regulated products: From Drugs benzene ring of a standard benzodiazepine but exhibit Prazepam and cosmetics to food and tobacco. Pacifici, E. and Bain, S., editors, 1st edition, Academic Press (2018). Acetylation similar activity and pharmacological effects. D Hydrolysis H Common opioids listed, more opioids and their metabolites and internal standards (MW plus 42) © Cayman Chemical Company · Created June 2019 available online Visit www.caymanchem.com/literature 2020 CAYMAN CHEMICAL · 1180 EAST ELLSWORTH ROAD · ANN ARBOR, MI 48108 · USA · (800) 364-9897 WWW.CAYMANCHEM.COM Stimulant and Hallucinogen CRMs Item No. Product Name Item No. Product Name ISO60188 (±)-Amphetamine (hydrochloride) (CRM) 26615 (+)-Methamphetamine (hydrochloride) (CRM) 25523 BZP (hydrochloride) (CRM) 20891 Methylone (hydrochloride) (CRM) ISO60176 Cocaine (CRM) 26279 Mexedrone (hydrochloride) (CRM) 25688 Deschloroketamine (hydrochloride) (CRM) ISO60194 PCP (hydrochloride) (CRM) 27239 bk-DMBDB (hydrochloride) (CRM) 28958 3-methoxy PCP (hydrochloride) (CRM) 29672 Eutylone (hydrochloride) (CRM) 25670 4-methyl Pentedrone (hydrochloride) (CRM) 19389 Ketamine (hydrochloride) (CRM) 27504 Pentylone (hydrochloride) (CRM) ISO60189 (±)-MDA (hydrochloride) (CRM) 24337 N-ethyl Pentylone (hydrochloride) (CRM) 27240 bk-MDEA (hydrochloride) (CRM) 22808 α-Pyrrolidinopentiophenone (hydrochloride) (CRM) ISO60190 3,4-MDMA (hydrochloride) (CRM) 28879 4'-chloro-α-Pyrrolidinovalerophenone (hydrochloride) (CRM) Common psychoactives listed, more psychoactive drugs and their metabolites and internal standards available online Synthetic Cannabinoid CRMs Item No. Product Name Item No. Product Name 27237 AB-CHMINACA (CRM) 17726 5-fluoro CUMYL-PINACA (CRM) ISO60211 AB-FUBINACA (CRM) 27973 JWH 018 (CRM) 19805 4-fluoro ADB (CRM) 22047 MAB-CHMINACA (CRM) 25012 (S)-5-fluoro ADB (CRM) 28186 4-fluoro MDMB-BUTINACA (CRM) 27043 AM2201 (CRM) 18203 PB-22 (CRM) 28624 APP-BUTINACA (CRM) ISO60059 XLR11 (CRM) Common synthetic cannabinoids listed, more synthetic cannabinoids and their metabolites and internal standards available online Sedative and Muscle Relaxant CRMs Barbiturate CRMs Item No. Product Name Item No. Product Name ISO60206 Carisoprodol (CRM) 22912 Amobarbital (CRM) ISO60141 Dextromethorphan (CRM) 22854 Barbital (CRM) 20283 Methaqualone (CRM) 20091 Butalbital (CRM) 20411 Zaleplon (CRM) 20966 Pentobarbital (CRM) 20648 Zolpidem (CRM) 20987 Phenobarbital (CRM) 20397 Zopiclone (CRM) 21707 Secobarbital (CRM) View a full list of internal standards online View a full list of internal standards online Antidepressant CRMs Performance-Enhancing Drug CRMs Item No. Product Name Item No. Product Name 19031 Amitriptyline (hydrochloride) (CRM) ISO60161 Androstenedione (CRM) 25576 Bupropion (hydrochloride) (CRM) 19247 Lorcaserin (hydrochloride) (CRM) 23981 Quetiapine (hemifumarate) (CRM) 21677 Methyldienolone (CRM) 19049 Trazodone (hydrochloride) (CRM) ISO60154 Testosterone (CRM) 25524 Venlafaxine (hydrochloride) (CRM) 9002564 11-keto Testosterone (CRM) View a full list of internal standards online To view a complete list of our Certified Reference Materials, visit us online at www.caymanchem.com/forensics 2020 CAYMAN CHEMICAL · 1180 EAST ELLSWORTH ROAD · ANN ARBOR, MI 48108 · USA · (800) 364-9897 WWW.CAYMANCHEM.COM.
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  • Title Continuation and Discontinuation of Benzodiazepine Prescriptions: A

    Title Continuation and Discontinuation of Benzodiazepine Prescriptions: A

    Continuation and discontinuation of benzodiazepine Title prescriptions: A cohort study based on a large claims database in Japan( Dissertation_全文 ) Author(s) Takeshima, Nozomi Citation 京都大学 Issue Date 2016-05-23 URL https://doi.org/10.14989/doctor.k19890 Right Type Thesis or Dissertation Textversion ETD Kyoto University Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎ Contents lists available at ScienceDirect Psychiatry Research journal homepage: www.elsevier.com/locate/psychres Continuation and discontinuation of benzodiazepine prescriptions: A cohort study based on A large claims database in Japan Nozomi Takeshima, Yusuke Ogawa, Yu Hayasaka, Toshi A Furukawa n Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan article info abstract Article history: Although benzodiazepines (BZDs) are often prescribed to treat a wide range of psychiatric and neuro- Received 29 March 2015 logical conditions, they are also associated with various harms and risks including dependence. However Received in revised form the frequency of its continued use in the real world has not been well studied, especially at longer follow- 15 October 2015 ups. The aim of this study was to clarify the frequency of long-term BZD use among new BZD users over Accepted 15 January 2016 longer follow-ups and to identify its predictors. We conducted a cohort study to examine how frequently new BZD users became chronic users, based on a large claims database in Japan from January 2005 to Keywords: June 2014. We used Cox proportional hazards models to identify potential predictors. A total 84,412 Benzodiazepine patients with new BZD prescriptions were included in our cohort.
  • PMDA Alert for Proper Use of Drugs When Using Benzodiazepine

    PMDA Alert for Proper Use of Drugs When Using Benzodiazepine

    ■ PMDA Alert for Proper Use of Drugs https://www.pmda.go.jp/english/safety/info-services/drugs/properly- No. 11 March 2017 use-alert/0001.html PMDA Alert for Proper Use of Drugs Pharmaceuticals and Medical Devices Agency No. 11 March 2017 Dependence associated with Benzodiazepine Receptor Agonists [To Patients] This document is for healthcare professionals. If taking the drug, please consult with your physicians or pharmacists. Please don’t reduce the dosage or stop taking the drug on self-judgment. Benzodiazepine receptor agonists have a characteristic of developing physical dependence with long-term use even within an approved dose range, leading to various withdrawal symptoms on dose reduction or discontinuation. <Major withdrawal symptoms> insomnia, anxiety, feeling irritated, headache, queasy/vomiting, delirium, tremor, seizure, etc. Please pay careful attention to the following when using benzodiazepine receptor agonists as hypnotics-sedatives and anxiolytics. Healthcare professionals should avoid long-term use with chronic administration. - Dependence may occur with long-term use even within an approved dose range. - Therapeutic necessity should be carefully considered when continuing administration of the drug. Healthcare professionals should adhere to the dosage and confirm that there is no multiple prescription of similar drugs. - Long-term administration, high-dose administration, or multiple medications increase the risk of developing dependence. - Healthcare professionals should confirm that similar drugs are not prescribed by other medical institutions. Healthcare professionals should reduce the dose or discontinue carefully such as by gradual dose reduction or alternate-days administration when discontinuing the administration. - Sudden discontinuation will develop serious withdrawal symptoms in addition to aggravate primary diseases.