DOCSLIB.ORG

II.3.4 Benzodiazepines by Hiroshi Seno and Hideki Hattori

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
II.3.4 Benzodiazepines by Hiroshi Seno and Hideki Hattori 3.4 II.3.4 Benzodiazepines by Hiroshi Seno and Hideki Hattori Introduction Benzodiazepines show antianxiety, hypnotic, anticonvulsant and muscle-relaxant eff ects. Th is group of drugs has wide safety dose ranges; it means that the ratio of the LD50 to the ED50 (therapeutic index) is high. Because of its safety, benzodiazepines are being widely used in the world. Some of benzodiazepines are also being abused or used for so-called “ drug facilitated sexual assault”, and thus they are under the control of the Narcotics and Psychotropics Control Law; in Japan, triazolam abuse has become one of the serious social problems. In this chapter, a GC/MS method for simultaneous analysis of 22 kinds of benzodiazepines listed in > Table 4.1 is described. In addition, the LC/MS analysis of triazolam, and its metabolites 4-hydroxy- triazolam and α-hydroxytriazolam is also presented. GC/MS analysis of benzodiazepines in blood and urine Reagents and their preparation • Th e pure powder of the 22 kinds of benzodiazepines was donated by each pharmaceutical manufacturers according to the authors’ request a (some of benzodiazepines now obtaina- ble from Sigma, St. Louis, MO, USA). • 1 M Sodium bicarbonate solution: a 8.4-g aliquot of sodium bicarbonate is dissolved in distilled water to prepare 100 mL solution. • 2 M Sodium acetate solution: a 27.5-g aliquot of sodium acetate is dissolved in distilled water to prepare 100 mL solution. GC/MS conditions Column: a DB-5 fused silica capillary column (30 m × 0.25 mm i.d., fi lm thickness 0.25 µm, J & W Scientifi c, Folsom, CA, USA). GC conditions; instrument: a GC-17A gas chromatograph (Shimadzu Corp., Kyoto, Japan); column (oven) temperature: 150 °C (1 min) → 20 °C/min → 300 °C (6.5 min); injection tempera- ture: 250 °C; carrier gas: He; its fl ow rate: 0.9 mL/min; sample injection: splitless mode for 1 min, followed by the split mode. MS conditions: a QP-5050A mass spectrometer (Shimadzu Corp.); ionization: EI; electron energy 70 eV; interface temperature: 250 °C. © Springer-Verlag Berlin Heidelberg 2005 284 Benzodiazepines ⊡ Table 4.1 Chemical structures of benzodiazepines Compound R1 R2 R3 R4 diazepam Cl CH3 H– fludiazepam Cl CH3 F– flurazepam Cl C2H5 F– (CH2)2N C2H5 prazepam Cl CH2 7◃ H– flutoprazepam Cl CH2 7◃ F– dipotassium Cl H H 3: CHCOOK clorazepate medazepam Cl CH3 H 2: CH2 clordiazepoxide Cl – H 2: CNHCH3; 4: N→O nitrazepam NO2 HH– nimetazepam NO2 CH3 H– clonazepam NO2 HCl– flunitrazepam NO2 CH3 F– bromazepam Br H – 5: C-pyridine tofisopam CH3CO – H 1: CHC2H5; 2: C–CH3; 3: N; 3’: –OCH3; 4’: –OCH3; 8: –COCH3 oxazolam Cl H H 4, 5: 2-methyloxazolo mexazolam Cl H Cl 4, 5: 3-methyloxazolo estazolam Cl – H 1, 2: triazolo alprazolam Cl – H 1, 2: 1-methyltriazolo triazolam Cl – Cl 1, 2: 1-methyltriazolo midazolam Cl – F 1, 2: 1-methyltriazolo etizolam – – Cl 1, 2: 1-methyltriazolo; 1, 5: 7-ethylthieno brotizolam – – Cl 1, 2: 1-methyltriazolo; 1, 5: 7-bromothieno GC/MS analysis of benzodiazepines in blood and urine 285 Procedure i. A 1-mL volume of whole blood or urine is mixed well with 8.5 mL distilled warter b in a 15-mL volume glass centrifuge tube with a ground-in stopper, followed by addition of 0.5 mL of 1 M sodium bicarbonate solution. ii. Aft er it is vortex-mixed, it is centrifuged at 3,000 rpm for 10 min to obtain a supernatant fraction. iii. An Oasis HLB 3cc solid-phase extraction cartridge (Waters, Milford, MA, USA) is set on a vacuum manifold, and 3 mL methanol and 3 mL water are passed through the cartridge for conditioningc. iv. Th e supernatant fraction prepared at the step ii) is loaded on the Oasis HLB cartridge c. v. Th e cartridge is washed with 3 mL distilled water d. vi. A target drug is eluted with 3 mL chloroform c into a 5-mL volume glass tube with a conical bottom. vii. Th e chloroform layer (lower phase) is carefully transferred to a 4-mL volume glass vial using a Pasteur pipette. viii. Th e organic layer is evaporated to dryness under a stream of nitrogen. ix. Th e residue is dissolved in 50 µL methanol and a 2-µL aliquot is injected into GC/MSe. Assessment and some comments on the method Th e recovery rates of the drugs from blood and urine were not less than 60 %. > Figure 4.1 shows a total ion chromatogram (TIC) for the authentic standards of benzodiazepines dis- solved in methanol. In this chromatogram, separation between dipotassium clorazepate and ⊡ Figure 4.1 TIC for the authentic standards of 22 benzodiazepines. 1: medazepam, 2: fludiazepam, 3: diazepam, 4: dipotassium clorazepate, 5: chlordiazepoxide, 6: oxazolam, 7: midazolam, 8: flunitrazepam, 9: flutoprazepam, 10: bromazepam, 11: prazepam, 12: nimetazepam, 13: mexazolam, 14: flurazepam, 15: nitrazepam, 16: clonazepam, 17: estazolam, 18: alprazolam, 19: tofisopam, 20: etizolam, 21: triazolam, 22: brotizolam. 286 Benzodiazepines chlordizepoxide, between fl utoprazepam and bromazepam and between fl urazepam and nitrazepam could not be achieved; the peak of tofi sopam showed tailing. Th e separation of other drugs was relatively good. Th e retention times, molecular weights and principal mass spectral ions of benzodiazepines are shown in > Table 4.2. Th e quantitatione of the drugs was made by selected ion monitoring (SIM). Excellent quan- titativeness could be confi rmed in the range of 10–1,000 ng/mL of diazepam, fl udiazepam, fl urazepam, prazepam, fl utoprazepam, dipotassium clorazepate, medazepam, chlordiazepoxide, fl unitrazepam, alprazolam, midazolam, etizolam and brotizolam for both blood and urine. Th e detection limits of these 13 drugs were 1–5 ng/mL. For nitrazepam, mexazolam, nimetazepam, clonazepam, bromazepam, tofi sopam, estazolam and triazolam, quantitativeness could be observed in the range of 50–1,000 ng/mL with detection limits of 10–20 ng/mL, and for oxa- zolam it could be observed in the range of 200–1,000 ng/mL with detection limits of 50 ng/mL in urine and 100 ng/mL in blood. ⊡ Table 4.2 Retention times and principal mass spectral ions of benzodiazepines measured by GC/MS Compound Retention Moleculer Principal ions m/z (% intensity) time (min) weight medazepam 7.97 270 207 (100), 242 (91), 244 (30), 270 (20),165 (15) fludiazepam 8.68 302 274 (100), 301 (96), 302 (92), 109 (43), 283 (37) diazepam 8.94 284 283 (100), 256 (94), 284 (88), 221 (36), 110 (31) dipotassium 9.28 409 242 (100), 270 (69), 103 (34), 89 (33), 76 (30) clorazepate chlordiazepoxide 9.31 299 282 (100), 124 (20), 247 (16), 220 (14), 89 (11) oxazolam 9.72 328 251 (100), 253 (30), 70 (30), 105 (13), 77 (12) midazolam 9.78 325 310 (100), 312 (30), 325 (20), 163 (12), 111 (12) flunitrazepam 9.91 313 285 (100), 312 (99), 313 (95), 266 (58), 238 (37) flutoprazepam 10.00 342 55 (100), 313 (67), 109 (61), 287 (42), 259 (37), 342 (29) bromazepam 10.01 315 90 (100), 326 (92), 315 (91), 77 (91), 317 (86) prazepam 10.10 324 55 (100), 91 (91), 269 (75), 295 (68), 324 (46) 241 (36) nimetazepam 10.30 295 267 (100), 294 (77), 248 (63), 295 (62), 220 (34) mexazolam 10.75 363 251 (100), 253 (30), 70 (22), 139 (11), 236 (9) flurazepam 10.83 387 86 (100), 99 (7), 58 (6), 387 (2) nitrazepam 10.91 281 280 (100), 253 (95), 234 (80), 264 (61), 206 (58) clonazepam 11.56 315 280 (100), 314 (87), 315 (68), 288 (54), 89 (52) estazolam 12.03 294 259 (100), 293 (65), 294 (64), 205 (59), 89 (50) alprazolam 12.42 308 279 (100), 273 (90), 308 (88), 204 (84), 102 (82) tofisopam 12.97 382 382 (100), 326 (87), 341 (63), 353 (33), 156 (31) etizolam 13.32 342 342 (100), 344 (47), 313 (37), 266 (31), 125 (24) triazolam 13.50 342 313 (100), 315 (76), 238 (71), 75 (62), 342 (52) brotizolam 13.82 392 394 (100), 392 (77), 245 (43), 118 (38), 123 (27) * The ions used for SIM are shown in boldfaces. LC/MS analysis of triazolam and its metabolites 287 In the analysis of benzodiazepines by GC and GC/MS, the decomposition of drugs due to heat frequently takes place. Th e decomposition is marked especially for oxazolam, cloxazolam, mexazolam, fl utazolam and haloxazolam having oxazolo rings in their structures [1]. In such cases, the relatively low injection temperature and the use of a wide-bore capillary column with short length (15 m) can protect the drugs from their heat decomposition to some extent. For nitro-group containing drugs, such as nitrazepam, nimetazepam, clonazepam and fl unitrazepam, the nitro group is rapidly metabolized into an amino group (in the 7-position) aft er being absorbed into human body [2]. Th e above GC/MS method deals with detection and identifi cation of unchanged benzodi- azepines. To detect benzodiazepine metabolites from urine specimens, it is necessary to hydro- lyze the glucuronate conjugates of the drugs using β-glucuronidase; the resulting free forms with hydroxyl groups should be derivatized before GC (/MS) analysis. When benzodiazepines are treated in strong acid, they are hydrolyzed into benzophenones, which are very stable against heat; the benzophenones can be also obtained from the hydroxyl- ated metabilites and their conjugates together with unchanged forms of benzodiazepines [3–5]. Using the benzophenone, detection and identifi cation of a benzodiazepine or its metabolites can be achieved by GC or GC/MS without any derivatization. However, it should be noted that an unchanged benzodiazepine, its hydroxylated metabolite and its glucuronide metabolite all give the same benzophenone; also there are many cases in which diff erent benzodiazepines give the same benzophenone.
Load more

Recommended publications
  • GABA Receptors
    D Reviews • BIOTREND Reviews • BIOTREND Reviews • BIOTREND Reviews • BIOTREND Reviews Review No.7 / 1-2011 GABA receptors Wolfgang Froestl , CNS & Chemistry Expert, AC Immune SA, PSE Building B - EPFL, CH-1015 Lausanne, Phone: +41 21 693 91 43, FAX: +41 21 693 91 20, E-mail: [email protected] GABA Activation of the GABA A receptor leads to an influx of chloride GABA ( -aminobutyric acid; Figure 1) is the most important and ions and to a hyperpolarization of the membrane. 16 subunits with γ most abundant inhibitory neurotransmitter in the mammalian molecular weights between 50 and 65 kD have been identified brain 1,2 , where it was first discovered in 1950 3-5 . It is a small achiral so far, 6 subunits, 3 subunits, 3 subunits, and the , , α β γ δ ε θ molecule with molecular weight of 103 g/mol and high water solu - and subunits 8,9 . π bility. At 25°C one gram of water can dissolve 1.3 grams of GABA. 2 Such a hydrophilic molecule (log P = -2.13, PSA = 63.3 Å ) cannot In the meantime all GABA A receptor binding sites have been eluci - cross the blood brain barrier. It is produced in the brain by decarb- dated in great detail. The GABA site is located at the interface oxylation of L-glutamic acid by the enzyme glutamic acid decarb- between and subunits. Benzodiazepines interact with subunit α β oxylase (GAD, EC 4.1.1.15). It is a neutral amino acid with pK = combinations ( ) ( ) , which is the most abundant combi - 1 α1 2 β2 2 γ2 4.23 and pK = 10.43.
    [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]
  • Analysis of a Benzodiazepine-Based Drug Using GC-MS 28
    LAAN-E-MS-E028 GCMS Gas Chromatograph Mass Spectrometer Analysis of a Benzodiazepine-Based Drug Using GC-MS 28 Benzodiazepine drugs are commonly used in sleeping aids and tranquilizers, and sometimes in crimes or suicide. Therefore, these chemical substances are often analyzed by forensic laboratories for criminal or academic investigations. This datasheet shows the results from using GC-MS to measure 9 types of benzodiazepine drugs. Analysis Conditions Table 1: Analysis Conditions GC-MS :GCMS-QP2010 Ultra Column : Rxi®-5Sil MS （30 mL. X 0.25 mmI.D., df=0.25 µm, Shimadzu GLC P/N:13623) Glass insert :Silanized splitless insert (P/N: 221-48876-03) [GC] [MS] Vaporization chamber temperature : 260℃ Interface temperature : 280℃ Column oven temperature : 60℃ (2min) -> (10℃/min) -> 320℃ (10min) Ion source temperature : 200℃ Injection mode : Splitless Solvent elution time : 2.0 min Sampling time : 1 min Measurement mode : Scan High pressure injection method: 250 kPa (1.5 min) Mass range : m/z 35-600 Carrier gas : Helium Event time : 0.3 sec Control mode :Linear velocity (45.6 cm/sec) Emission current : 150 µA (high sensitivity) Purge flow rate :3.0 ml/min Sample injection quantity :1.0 µL (x1,000,000) 3.0 3 2.5 2 2.0 1.5 1.0 1 0.5 22.0 23.0 24.0 25.0 26.0 27.0 28.0 min % % 312 55 100.0 1 285 100.0 2 313 109 75.0 75.0 266 259287 342 166 50.0 238 50.0 248 25.0 183 25.0 63 109 0.0 0.0 100 200 300 400 100 200 300 400 % 86 100.0 3 75.0 50.0 25.0 58 99 183 315 387 0.0 100 200 300 400 Fig.
    [Show full text]
  • Benzodiazepine Group ELISA Kit
    Benzodiazepine Group ELISA Kit Benzodiazepine Background Since their introduction in the 1960s, benzodiazepines have been widely prescribed for the treatment of anxiety, insomnia, muscle spasms, alcohol withdrawal, and seizure-prevention as they are depressants of the central nervous system. Despite the fact that they are highly effective for their intended use, benzodiazepines are prescribed with caution as they can be highly addictive. In fact, researchers at NIDA (National Institute on Drug Abuse) have shown that addiction for benzodiazepines is similar to that of opioids, cannabinoids, and GHB. Common street names of benzodiazepines include “Benzos” and “Downers”. The five most encountered benzodiazepines on the illicit market are alprazolam (Xanax), lorazepam (Ativan), clonazepam (Klonopin), diazepam (Valium), and temazepam (Restori). The method of abuse is typically oral or snorted in crushed form. The DEA notes a particularly high rate of abuse among heroin and cocaine abusers. Designer benzodiazepines are currently offered in online shops selling “research chemicals”, providing drug abusers an alternative to prescription-only benzodiazepines. Data defining pharmacokinetic parameters, drug metabolisms, and detectability in biological fluids is limited. This lack of information presents a challenge to forensic laboratories. Changes in national narcotics laws in many countries led to the control of (phenazepam and etizolam), which were marketed by pharmaceutical companies in some countries. With the control of phenazepam and etizolam, clandestine laboratories have begun researching and manufacturing alternative benzodiazepines as legal substitutes. Delorazepam, diclazepam, pyrazolam, and flubromazepam have emerged as compounds in this class of drugs. References Drug Enforcement Administration, Office of Diversion Control. “Benzodiazepines.” http://www.deadiversion.usdoj.gov/drugs_concern/benzo_1.
    [Show full text]
  • Recommended Methods for the Identification and Analysis of Fentanyl and Its Analogues in Biological Specimens
    Recommended methods for the Identification and Analysis of Fentanyl and its Analogues in Biological Specimens MANUAL FOR USE BY NATIONAL DRUG ANALYSIS LABORATORIES Laboratory and Scientific Section UNITED NATIONS OFFICE ON DRUGS AND CRIME Vienna Recommended Methods for the Identification and Analysis of Fentanyl and its Analogues in Biological Specimens MANUAL FOR USE BY NATIONAL DRUG ANALYSIS LABORATORIES UNITED NATIONS Vienna, 2017 Note Operating and experimental conditions are reproduced from the original reference materials, including unpublished methods, validated and used in selected national laboratories as per the list of references. A number of alternative conditions and substitution of named commercial products may provide comparable results in many cases. However, any modification has to be validated before it is integrated into laboratory routines. ST/NAR/53 Original language: English © United Nations, November 2017. All rights reserved. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. Mention of names of firms and commercial products does not imply the endorse- ment of the United Nations. This publication has not been formally edited. Publishing production: English, Publishing and Library Section, United Nations Office at Vienna. Acknowledgements The Laboratory and Scientific Section of the UNODC (LSS, headed by Dr. Justice Tettey) wishes to express its appreciation and thanks to Dr. Barry Logan, Center for Forensic Science Research and Education, at the Fredric Rieders Family Founda- tion and NMS Labs, United States; Amanda L.A.
    [Show full text]
  • Control Substance List
    Drugs DrugID SubstanceName DEANumbScheNarco OtherNames 1 1-(1-Phenylcyclohexyl)pyrrolidine 7458 I N PCPy, PHP, rolicyclidine 2 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine 9663 I Y PEPAP, synthetic heroin 3 1-[1-(2-Thienyl)cyclohexyl]piperidine 7470 I N TCP, tenocyclidine 4 1-[1-(2-Thienyl)cyclohexyl]pyrrolidine 7473 I N TCPy 5 13Beta-ethyl-17beta-hydroxygon-4-en-3-one 4000 III N 6 17Alpha-methyl-3alpha,17beta-dihydroxy-5alpha-androstane 4000 III N 7 17Alpha-methyl-3beta,17beta-dihydroxy-5alpha-androstane 4000 III N 8 17Alpha-methyl-3beta,17beta-dihydroxyandrost-4-ene 4000 III N 9 17Alpha-methyl-4-hydroxynandrolone (17alpha-methyl-4-hyd 4000 III N 10 17Alpha-methyl-delta1-dihydrotestosterone (17beta-hydroxy- 4000 III N 17-Alpha-methyl-1-testosterone 11 19-Nor-4-androstenediol (3beta,17beta-dihydroxyestr-4-ene; 4000 III N 12 19-Nor-4-androstenedione (estr-4-en-3,17-dione) 4000 III N 13 19-Nor-5-androstenediol (3beta,17beta-dihydroxyestr-5-ene; 4000 III N 14 19-Nor-5-androstenedione (estr-5-en-3,17-dione) 4000 III N 15 1-Androstenediol (3beta,17beta-dihydroxy-5alpha-androst-1- 4000 III N 16 1-Androstenedione (5alpha-androst-1-en-3,17-dione) 4000 III N 17 1-Methyl-4-phenyl-4-propionoxypiperidine 9661 I Y MPPP, synthetic heroin 18 1-Phenylcyclohexylamine 7460 II N PCP precursor 19 1-Piperidinocyclohexanecarbonitrile 8603 II N PCC, PCP precursor 20 2,5-Dimethoxy-4-(n)-propylthiophenethylamine 7348 I N 2C-T-7 21 2,5-Dimethoxy-4-ethylamphetamine 7399 I N DOET 22 2,5-Dimethoxyamphetamine 7396 I N DMA, 2,5-DMA 23 3,4,5-Trimethoxyamphetamine
    [Show full text]
  • 124.210 Schedule IV — Substances Included. 1
    1 CONTROLLED SUBSTANCES, §124.210 124.210 Schedule IV — substances included. 1. Schedule IV shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. 2. Narcotic drugs. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation containing any of the following narcotic drugs, or their salts calculated as the free anhydrous base or alkaloid, in limited quantities as set forth below: a. Not more than one milligram of difenoxin and not less than twenty-five micrograms of atropine sulfate per dosage unit. b. Dextropropoxyphene (alpha-(+)-4-dimethylamino-1,2-diphenyl-3-methyl-2- propionoxybutane). c. 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol, its salts, optical and geometric isomers and salts of these isomers (including tramadol). 3. Depressants. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances, including its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation: a. Alprazolam. b. Barbital. c. Bromazepam. d. Camazepam. e. Carisoprodol. f. Chloral betaine. g. Chloral hydrate. h. Chlordiazepoxide. i. Clobazam. j. Clonazepam. k. Clorazepate. l. Clotiazepam. m. Cloxazolam. n. Delorazepam. o. Diazepam. p. Dichloralphenazone. q. Estazolam. r. Ethchlorvynol. s. Ethinamate. t. Ethyl Loflazepate. u. Fludiazepam. v. Flunitrazepam. w. Flurazepam. x. Halazepam. y. Haloxazolam. z. Ketazolam. aa. Loprazolam. ab. Lorazepam. ac. Lormetazepam. ad. Mebutamate. ae. Medazepam. af. Meprobamate. ag. Methohexital. ah. Methylphenobarbital (mephobarbital).
    [Show full text]
  • S1 Table. List of Medications Analyzed in Present Study Drug
    S1 Table. List of medications analyzed in present study Drug class Drugs Propofol, ketamine, etomidate, Barbiturate (1) (thiopental) Benzodiazepines (28) (midazolam, lorazepam, clonazepam, diazepam, chlordiazepoxide, oxazepam, potassium Sedatives clorazepate, bromazepam, clobazam, alprazolam, pinazepam, (32 drugs) nordazepam, fludiazepam, ethyl loflazepate, etizolam, clotiazepam, tofisopam, flurazepam, flunitrazepam, estazolam, triazolam, lormetazepam, temazepam, brotizolam, quazepam, loprazolam, zopiclone, zolpidem) Fentanyl, alfentanil, sufentanil, remifentanil, morphine, Opioid analgesics hydromorphone, nicomorphine, oxycodone, tramadol, (10 drugs) pethidine Acetaminophen, Non-steroidal anti-inflammatory drugs (36) (celecoxib, polmacoxib, etoricoxib, nimesulide, aceclofenac, acemetacin, amfenac, cinnoxicam, dexibuprofen, diclofenac, emorfazone, Non-opioid analgesics etodolac, fenoprofen, flufenamic acid, flurbiprofen, ibuprofen, (44 drugs) ketoprofen, ketorolac, lornoxicam, loxoprofen, mefenamiate, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, pranoprofen, proglumetacin, sulindac, talniflumate, tenoxicam, tiaprofenic acid, zaltoprofen, morniflumate, pelubiprofen, indomethacin), Anticonvulsants (7) (gabapentin, pregabalin, lamotrigine, levetiracetam, carbamazepine, valproic acid, lacosamide) Vecuronium, rocuronium bromide, cisatracurium, atracurium, Neuromuscular hexafluronium, pipecuronium bromide, doxacurium chloride, blocking agents fazadinium bromide, mivacurium chloride, (12 drugs) pancuronium, gallamine, succinylcholine
    [Show full text]
  • Drug Screening: Actual Status, Pitfalls and Suggestions for Improvement Drogenscreening: Gegenwa¨ Rtiger Stand, Fehlermo¨ Glichkeiten Und Verbesserungsvorschla¨Ge
    J Lab Med 2004;28(4):317–325 ᮊ 2004 by Walter de Gruyter • Berlin • New York 2004/03304 Drug Monitoring und Toxikologie Redaktion: V. W. Armstrong Drug screening: Actual status, pitfalls and suggestions for improvement Drogenscreening: Gegenwa¨ rtiger Stand, Fehlermo¨ glichkeiten und Verbesserungsvorschla¨ge Wolf R. Ku¨ lpmann* pretierbar. In Wirklichkeit mu¨ ssen viele Aspekte beru¨ ck- sichtigt werden, um einen aussagekra¨ ftigen Befund zu Klinische Chemie, Medizinische Hochschule Hannover, erhalten, z.B. Pra¨ analytik, Spezifita¨ t und Empfindlichkeit Hannover, Germany des Verfahrens oder Qualita¨ tssicherung. Obwohl die Abstract mechanisierten Meßverfahren naturgema¨ ß quantitative Ergebnisse liefern, wird aufgezeigt, daß es sich in der Immunoassays for drug screening are often regarded as Regel empfiehlt, qualitative Befunde zu erstellen. Die procedures which are easily performed and interpreted. Verfahren erlauben aber im Gegensatz zu den auch fu¨r But in fact, many aspects have to be considered to diese Zwecke verwendeten Teststreifen die Entschei- obtain a meaningful result. Among these are sampling, dungsgrenze (cut-off) der jeweiligen Fragestellung anzu- specificity and sensitivity of assays, and quality assess- passen, z.B. bei akuter Intoxikation, chronischem Abusus ment. Although the mechanised procedures yield quan- oder U¨ berwachung des Drogenentzugs. titative results, there are good reasons to generally report Ein schwerwiegender Nachteil von Immunoassays zum qualitative findings. The mechanised procedures allow Nachweis von Amphetamin und a¨ hnlichen Substanzen, the adjustment of the cut-off concentration to the clinical Barbituraten, Benzodiazepinen und Opiaten besteht dar- setting, e.g. in the case of acute intoxication, chronic in, daß eine starke Kreuzreaktivita¨ t des Antiko¨ rpers abuse or drug withdrawal, an important advantage as gegenu¨ ber pharmakologisch wenig wirksamen Verbin- compared to test strips.
    [Show full text]
  • Statistical Analysis Plan Statistical Center for HIV/AIDS Research & SCHARP Prevention SD Standard Deviation SI International System of Units
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able of contents 1. INTRODUCTION ........................................................................................................9 1.1. Study Objectives ...........................................................................................................9 1.2. Study Design ...............................................................................................................10 1.2.1. Determination of Sample Size ....................................................................................11 1.2.2. Randomization and Blinding ......................................................................................11 2. ANALYSES PLANNED ............................................................................................12 2.1. General Analysis Definition .......................................................................................12 2.1.1. Logic
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2009/0005722 A1 Jennings-Spring (43) Pub
    US 20090005722A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0005722 A1 Jennings-Spring (43) Pub. Date: Jan. 1, 2009 (54) SKIN-CONTACTING-ADHESIVE FREE Publication Classification DRESSING (51) Int. Cl. Inventor: Barbara Jennings-Spring, Jupiter, A61N L/30 (2006.01) (76) A6F I3/00 (2006.01) FL (US) A6IL I5/00 (2006.01) Correspondence Address: AOIG 7/06 (2006.01) Irving M. Fishman AOIG 7/04 (2006.01) c/o Cohen, Tauber, Spievack and Wagner (52) U.S. Cl. .................. 604/20: 602/43: 602/48; 4771.5; Suite 2400, 420 Lexington Avenue 47/13 New York, NY 10170 (US) (57) ABSTRACT (21) Appl. No.: 12/231,104 A dressing having a flexible sleeve shaped to accommodate a Substantially cylindrical body portion, the sleeve having a (22) Filed: Aug. 29, 2008 lining which is substantially non-adherent to the body part being bandaged and having a peripheral securement means Related U.S. Application Data which attaches two peripheral portions to each other without (63) Continuation-in-part of application No. 1 1/434,689, those portions being circumferentially adhered to the sleeve filed on May 16, 2006. portion. Patent Application Publication Jan. 1, 2009 Sheet 1 of 9 US 2009/0005722 A1 Patent Application Publication Jan. 1, 2009 Sheet 2 of 9 US 2009/0005722 A1 10 8 F.G. 5 Patent Application Publication Jan. 1, 2009 Sheet 3 of 9 US 2009/0005722 A1 13 FIG.6 2 - Y TIII Till "T fift 11 10 FIG.7 8 13 6 - 12 - Timir" "in "in "MINIII.
    [Show full text]
  • Introduced B.,Byhansen, 16
    LB301 LB301 2021 2021 LEGISLATURE OF NEBRASKA ONE HUNDRED SEVENTH LEGISLATURE FIRST SESSION LEGISLATIVE BILL 301 Introduced by Hansen, B., 16. Read first time January 12, 2021 Committee: Judiciary 1 A BILL FOR AN ACT relating to the Uniform Controlled Substances Act; to 2 amend sections 28-401, 28-405, and 28-416, Revised Statutes 3 Cumulative Supplement, 2020; to redefine terms; to change drug 4 schedules and adopt federal drug provisions; to change a penalty 5 provision; and to repeal the original sections. 6 Be it enacted by the people of the State of Nebraska, -1- LB301 LB301 2021 2021 1 Section 1. Section 28-401, Revised Statutes Cumulative Supplement, 2 2020, is amended to read: 3 28-401 As used in the Uniform Controlled Substances Act, unless the 4 context otherwise requires: 5 (1) Administer means to directly apply a controlled substance by 6 injection, inhalation, ingestion, or any other means to the body of a 7 patient or research subject; 8 (2) Agent means an authorized person who acts on behalf of or at the 9 direction of another person but does not include a common or contract 10 carrier, public warehouse keeper, or employee of a carrier or warehouse 11 keeper; 12 (3) Administration means the Drug Enforcement Administration of the 13 United States Department of Justice; 14 (4) Controlled substance means a drug, biological, substance, or 15 immediate precursor in Schedules I through V of section 28-405. 16 Controlled substance does not include distilled spirits, wine, malt 17 beverages, tobacco, hemp, or any nonnarcotic substance if such substance 18 may, under the Federal Food, Drug, and Cosmetic Act, 21 U.S.C.
    [Show full text]