DOCSLIB.ORG

Rapid Quantification of Tilidine, Nortilidine and Bisnortilidine in Urine by Automated Online-SPE-LC-MS/MS

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Rapid Quantification of Tilidine, Nortilidine and Bisnortilidine in Urine by Automated Online-SPE-LC-MS/MS Institute of Toxicology Clinical Toxicology and Pharmacology LOGO Berliner Betrieb für Zentrale Gesundheitliche Aufgaben, Berlin Rapid Quantification of Tilidine, Nortilidine and Bisnortilidine in Urine by automated online-SPE-LC-MS/MS Christoph Köhler Thomas Grobosch Torsten Binscheck 48th Annual Meeting of the International Association of Forensic Toxicologists Conference in Bonn August 29 - September 2, 2010 introduction Tilidine O CH3 Synthetic opioid analgesic O CH3 N CH3 Strong analgesic effect of its main metabolite (+)-tilidine nortilidine [2]. Hepatically N-demethylation of tilidine to nortilidine O CH3 O and bisnortilidine (CYP3A4, CYP2C19, CYP2D6) [1] NH CH3 (+)-nortilidine In commercially available preparations tilidine is combined with the µ-opioid-receptor antagonist naloxone preventing opioid abuse [2]. HO O CH3 O O NH N 2 OH CH2 O (+)-bisnortilidine naloxone (1S,5 R,13 R,17 S) Source: [1] Clin. Chem. 24/2, 692-697 (1978) 2 [2] Fachinfo Valorone N®, Fa. Pfizer; 2008 introduction Aims Sensitive quantification of tilidine and its metabolites in urine samples No immunoassay for the detection of tilidine abuse is available! Offline-LLE LC QTrap Increasing number of samples (max. 100 samples/d!) consumed much time and human resources for the LLE (max. 180 min/d!). Online-SPE LC QTrap 3 introduction Online-SPE-LC Highly automated Chromatography sample preparation Analytical column: Automatization: Luna phenyl-hexyl 50x2 mm 5 µm 1. IS-mixing procedure Mobile phase: 2. Complete SPE procedure 0.2% FA + MeOH (gradient elution ) Total run time: 3.5 min Symbiosis Pico™ Spark Holland Online-SPE LC 4 SPE method development SPE Optimization Mix setup: 100 µL Aqueous analyte solution of tilidine, nortilidine and naloxone (c = 50 µg/L) + 100 µL 100 mM NH 4Ac-solution (pH 6); IS PCP-D5 (c=100 ng/mL) SPE sorbent: OASIS WCX 10x1mm Generic SPE procedure: volume flow rate SPE step solvent (µl) (ml/min) Conditioning MeOH 1500 5.0 Equilibration 1000 5.0 Loading 10 mM NH 4Ac-solution pH 6 500 0.5 Clean up 1000 1.0 Elution Mobile phase 1050 0.3 5 SPE method development SPE Optimization Mix setup: 100 µL Aqueous analyte solution of tilidine, nortilidine and naloxone (c = 50 µg/L) + 100 µL 100 mM NH 4Ac-solution (pH 6); IS PCP-D5 (c=100 ng/mL) SPE sorbent: OASIS WCX 10x1mm Generic SPE procedure: volume flow rate SPE step solvent (µl) (ml/min) Conditioning MeOH 1500 5.0 Equilibration 1000 5.0 10 mM NH 4Ac-solution pH 6 Loading 500 0.5 Clean up ?? 1.0 Elution Mobile phase ? 0.3 6 SPE method development Results (wash solution) Wash solution: 10 mM NH 4Ac-solution pH 6 + 0/10/15/20/40% MeOH 100 80 60 tilidine 40 nortilidine recovery (%) (%) recovery recovery naloxone 20 IS 0 0 10 20 30 40 MeOH in wash solution (%) Conclusion: 10% MeOH 7 SPE method development Results (wash volume) Wash solution: 10 mM NH 4Ac-solution pH 6 + 10% MeOH Wash volume: 500/1000/1500 µL 100 80 60 tilidine nortilidine 40 naloxone recovery (%) (%) recovery recovery IS 20 0 0 500 1000 1500 wash volume ( µl) Conclusion: 500 µL ≙ 60 bed volumes 8 SPE method development Results (elution volume) Wash solution: 10 mM NH 4Ac-solution pH 6 + 10% MeOH Elution volume: 150/300/600/900/1200 µL 100 80 60 tilidine nortilidine 40 recovery (%) (%) recovery recovery naloxone 20 IS 0 0 200 400 600 800 1000 1200 elution volume (µL) Conclusion: 600 µL ≙ 2 min elution time 9 SPE method development Final SPE method Mix setup: 100 µL sample (urine) + 100 µL 100 mM NH 4Ac-solution (pH 6); c(PCP-D5)=100 ng/mL SPE sorbent: OASIS WCX 10x1mm Generic SPE procedure: volume flow rate SPE step solvent (µl) (ml/min) Conditioning MeOH 1500 5.0 Equilibration 1000 5.0 10 mM NH 4Ac-solution pH 6 Loading 500 0.5 10 mM NH Ac-solution pH 6 + Clean up 4 500 (1000) 1.0 10% MeOH Elution Mobile phase 600 (1050) 0.3 10 Validation and routine work Validation data of the new method Calibration curves of the analytes Untitled 18 (Tilidin 1): "Linear Through Zero" Regression ("No" weighting): y = 0.0101 x (r = 0.9993) 1.00 Selectivity: 0.95 0.90 0.85 no interference by matrix peaks 0.80 0.75 0.70 tilidine 0.65 0.60 0.55 Ionsuppression: 0.50 0.45 0.40 Analyte Area / IS Area IS / Area Analyte 0.35 < 10% for all analytes 0.30 R = 0.9993 0.25 0.20 0.15 0.10 Recovery: 0.05 0.00 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 Analyte Conc. / IS Conc. > 80% for all analytes and IS Untitled 18 (Nortilidin 1): "Linear Through Zero" Regression ("No" weighting): y = 0.00911 x (r = 0.9992) 0.90 0.85 0.80 Intra -assay precision (n=6 per conc .): 0.75 0.70 0.65 0.60 nortilidine coefficient of variation: ≤ 6% 0.55 0.50 0.45 0.40 Inter-assay precision (n=6 per conc.): Area IS / Area Analyte 0.35 0.30 R = 0.9992 0.25 0.20 coefficient of variation: ≤ 7% 0.15 0.10 0.05 0.00 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 LLOQ : Analyte Conc. / IS Conc. Untitled 18 (Bisnortilidin 1): "Linear Through Zero" Regression ("No" weighting): y = 0.00635 x (r = 0.9996) 0.63 1.0 µg/L for all analytes 0.60 0.55 0.50 0.45 Linearity : 0.40 bisnortilidine 0.35 1.0-100 µg/L 0.30 Analyte Area / IS Area IS / Area Analyte 0.25 0.20 R = 0.9996 0.15 0.10 0.05 0.00 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 Analyte Conc. / IS Conc. Society of Toxicological and Forensic Chemistry (GTFCH) Guidance in forensic quality terms 11 Toxichem Krimtech 2009; 76 (3): 185 Implementation in routine Reduction of the manual preparation time by the factor 10 Positive result: c (tilidine) and c (nortilidine) > 1.0 µg/L (cutoff) or c ( nortilidine ) and c ( bisnortilidine ) > 1.0 µg/L (cutoff) Analysis of 3665 samples from correctional facilities: - 55 positive results (1.5 %) - positive samples: c (bisnortilidine) > c (nortilidine) → could the detection of bisnortilidine increase the drug detection window? 12 Tilidine Urinary Excretion of Tilidine A single oral dose of Valoron ®N solution (50 mg T-HCl and 4 mg NX-HCl) was administered to a male volunteer (age: 28 years; body height: 175 cm; body weight: 72 kg) Drug detection window g Analyte (d) - ß-glucuronidase + ß -glucuronidase Tilidine 4.5 4.5 Nortilidine 5.5 5.5 Bisnortilidine 6.8 7.8 positive result 5.5 5.5 13 Chromatograms 1.81 Concentration: N/A Concentration: N/A Calculated Conc: 14.5 ng/mL Calculated Conc: 1.66 ng/mL 1.00e5 2.0e4 Tilidine (c=7.63 µg/L) Bisnortilidine (c=96.5 µg/L) 8.00e4 1.5e4 → Proc. Algorithm: Analyst Classic m/z 246.1 →155.1 Proc. Algorithm: Analyst Classic m/z 274.2 155.1 6.00e4 1.0e4 Intensity, cps Intensity, 4.00e4 Intensity, cps Intensity, 5000.0 2.00e4 0.00 0.0 0.5 1.0 1.5 2.0 2.5 3.0 0.5 1.0 1.5 2.0 2.5 3.0 Time, min Time, min 1.81 Concentration: N/A Concentration: N/A 6.0e4 Calculated Conc: 1.80 ng/mL Calculated Conc: 14.7 ng/mL 2.05 7000 Bisnortilidine Tilidine 5.0e4 6000 → 4.0e4 m/z 246.1 229.2 5000 Proc. Algorithm: Analyst Classic m/z 274.2 →115.1 Proc. Algorithm: Analyst Classic 4000 3.0e4 3000 Intensity, cps Intensity, Intensity, cps Intensity, 2.0e4 2000 1.0e4 1000 0 0.0 0.5 1.0 1.5 2.0 2.5 3.0 0.5 1.0 1.5 2.0 2.5 3.0 Time, min Time, min 1.81 Concentration: N/A Calculated Conc: 5.44 ng/mL 6.0e4 5.0e4 Nortilidine (c=36.9 µg/L) Proc. Algorithm: Analyst Classic 4.0e4 m/z 260.2 →155.1 3.0e4 Intensity, cps Intensity, 2.0e4 1.0e4 0.0 0.5 1.0 1.5 2.0 2.5 3.0 Time, min Concentration: N/A Calculated Conc: 5.17 ng/mL 1.94 4000 Concentration: 1.00 ng/mL 7.0e5 Nortilidine Calculated Conc: N/A IS Phencyclidine-D5 (c=33.33 µg/L) 6.0e5 3000 m/z 249.3 →96.1 Proc. Algorithm: Analyst Classic m/z 260.2 →115.1 5.0e5 Proc. Algorithm: Analyst Classic 4.0e5 2000 Intensity, cps Intensity, 3.0e5 Intensity, cps Intensity, 1000 2.0e5 1.0e5 0 0.0 2.13 0.5 1.0 1.5 2.0 2.5 3.0 0.5 1.0 1.5 2.0 2.5 3.0 Time, min Time, min 14 Conclusion An highly sensitive method for the determination of tilidine, nortilidine and bisnortilidine in urine was developed and validated on an online- SPE-LC-QTrap Due to the automatization of the online -SPE the manual preparation time of the new method is 20 min/100 samples. 3665 authentic samples were analyzed resulting in 55 positive results. The LLOQ of 1 µg/L allowed detecting a single oral dose of a tilidine preparation up to 5 days after administration.
Load more

Recommended publications
  • Identifying New/Emerging Psychoactive Substances at the Time of COVID-19; a Web-Based Approach
    ORIGINAL RESEARCH published: 09 February 2021 doi: 10.3389/fpsyt.2020.632405 Identifying New/Emerging Psychoactive Substances at the Time of COVID-19; A Web-Based Approach Valeria Catalani 1*, Davide Arillotta 1, John Martin Corkery 1, Amira Guirguis 1,2, Alessandro Vento 3,4,5 and Fabrizio Schifano 1 1 Psychopharmacology, Drug Misuse & Novel Psychoactive Substances Research Unit, School of Life & Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom, 2 Swansea University Medical School, Institute of Life Sciences 2, Swansea University, Swansea, United Kingdom, 3 Department of Mental Health, ASL Roma 2, Rome, Italy, 4 Addictions’ Observatory (ODDPSS), Rome, Italy, 5 Department of Psychology, Guglielmo Marconi University, Rome, Italy COVID-19-related disruptions of people and goods’ circulation can affect drug markets, especially for new psychoactive substances (NPSs). Drug shortages could cause a change in available NPS, with the introduction of new, unknown, substances. The aims of the current research were to use a web crawler, NPSfinder®, to identify and categorize emerging NPS discussed on a range of drug enthusiasts/psychonauts’ websites/fora at the time of the pandemic; social media for these identified NPS were screened as Edited by: well. The NPSfinder® was used here to automatically scan 24/7 a list of psychonaut Ornella Corazza, University of Hertfordshire, websites and NPS online resources. The NPSs identified in the time frame between United Kingdom January and August 2020 were searched in both the European Monitoring Center Reviewed by: for Drugs and Drug Addictions (EMCDDA)/United Nations Office on Drugs and Crime Simona Zaami, Sapienza University of Rome, Italy (UNODC) databases and on social media (Facebook, Twitter, Instagram, Pinterest, Laura Hondebrink, and YouTube) as well, with a content qualitative analysis having been carried out on University Medical Center reddit.com.
    [Show full text]
  • XXI. Gtfch-Symposium Poster
    Toxichem Krimtech 2019;86(2):145 XXI. GTFCh-Symposium Poster P01 Impact of the NpSG on the number of hospitalisations due to NPS use Michaela Sommer1, Sebastian Halter1, Verena Angerer3, Volker Auwärter1, Maren Hermanns- Clausen2 1 Institut für Rechtsmedizin, Universitätsklinikum, Freiburg 2 Zentrum für Kinder- und Jugendmedizin, Vergiftungs-Informations-Zentrale, Universitätsklinikum, Freiburg 3 Institut für Rechtsmedizin, Kantonsspital St. Gallen, St. Gallen, Schweiz Aims: New psychoactive substances (NPS) have become a lasting threat to public health for many years. To prevent the emergence and spread of NPS, a new German law, the ‘NpSG’ (act on NPS), took effect in November 2016. This study presents an overview of analytically confirmed NPS intoxications during a 4-year period. To demonstrate effects of the act, the results of two years before and after the introduc- tion of the law were compared. Methods: Within the scope of a prospective observational study blood and urine samples were collected from emergency patients with suspected NPS intoxication. Compre- hensive drug analyses were performed by LC-MS/MS analysis. Results and Discussion: In the period considered, 137 patients were included. SC intake was verified in 63 cases (70%) in the 2-year period before and in 27 cases (77%) after the law change, respectively. Designer stimulants or hallucinogenic drugs were tested positive in 11 cases (12%) in the first period and in 15 cases (31%) in the second period. Since February 2017, four different SCs (cumyl-PEGACLONE, 5F-MDMB-P7AICA, EG-018, 5F-cumyl-P7AICA) not covered by the NpSG were detected in six cases. In the first period the most prevalent SC in the samples was MDMB-CHMICA (21 cases).
    [Show full text]
  • Respiratory Depression • • Loss of Consciousness Serotonergic Syndrome and • Constipation Nausea and Vomiting Convulsion
    Opioids in daily practice Dr Frédéric Lebrun Soins intensifs et urgences pédiatriques Unité pédiatrique de prise en charge de la douleur, CHC-Liège Belgian Paediatric Pain Association Fear of morphine and opioids ! Opioid Crisis in the US Opioids restrictions Restricting the use of codeine in children and breastfeeding women (2013) Restricting the use of tramadol in children and breastfeeding women (2017) Adverse opioids reactions Serotonic effect : • Respiratory depression • • Loss of consciousness Serotonergic syndrome and • Constipation Nausea and vomiting convulsion • Dry mouth Chronic opioid abuse : • Drowsiness • Tolerance • Pruritus • Dependence • Withdrawal • Addiction Opioids in my daily practice ? Serious ADRs ADRs very unlikely when opioids are titrated carefully ! Awareness of the possible sides effects should not lead to underuse of opioids ! Good practice guidelines • Multimodal approach : Non-phramacological Pharmacological • Best suited treatment to patient situation • Favor oral route (moderate pain) • Give at regular interval • Prevent procedural pain • Quickly adapt therapy according to resudal pain • Monitor and prevent adverse drug reactions (ADRs) • Use protocols Which analgesic medication ? Type of pain Patient’s condition Intensity ? Age ? Route ? Cormorbidities ? Fast onset ? Co-adminstrations ? Duration ? Setting of care ? Past-experience? Mecanism ? Hospital ? Home ? Which analgesic medication ? • Paracétamol • Benzodiazépines • AINS • Spasmolytiques • Morphiniques • Clonidine • Dexmédétomidine • Kétamine •
    [Show full text]
  • Club Drugs Wheel (Display Poster Version 1.0.4 • 30/08/2020)
    Club Drugs Wheel (Display poster version 1.0.4 • 30/08/2020) eartbeat, sweating ng h , en aci well-bein erg R nce, g, eu y y fide pho Be ep Con ppetite, clen ria lo le ed a ched ng s y wer jaw Co in , tch Lo upils, paranoia s nn g e i d p , an S e , af , ng late xie e ct s hi Di ings, arousal, im ty xu io u rm at sw pote S al n, n , a re aty ood nc w a d e w b e M A e ea ro e e sw l R t, u s r a MP i e s fr p , w sk w s r , aine a t o ia a Heroin a - t r MDPV Khat o r l o a le s r d one f m , 4F-MPH t n o th Methadone o n i b h i Coc t e i , A d h r n d a s p w eh , e c il u , Bupr MDMA i i p n e e MD yd o c n n i p c v t g , Ethylphenidate r e i v u a n F enorphine Mephedr a l , e entanyl Amphetamine t r e , t n p e d PMMA i h i s o s n n Morphine Methamphetamine n e d d u e / a y y e e a p PMA, o n e t s n t n e Methylone v , d g d Dihydr ButyloneAPB e f d c , o u e fi n i r r g , h v n i r AI 5/6- o r n l t e ocodeine y e n Tr 2- c m g i s amadol Kr d r o e s t Ethylone, t 2-MPPP d i o atom 3-FPM AI r i y e n 5/6-MAPB o C d a o e r MD F o m O-desmethyltr Isotonitazene t s n e i C o one 4,4’-DMAR A o e v V edr 4-MT n O U-47700 2-methyl x S amadol L a Me APDI O p h 4-MPM 5- M o s -bucinnazine Nicotine V t Caeine p i t g s m e Diazepam o o r a e n Nortilidine I x] u c s i m i o 5-IA 2C[- o n e n t o t 2CI, i d c 2CE, i u e i d k T 2CB, t o emazepam n , d i a c m 5-MeO-DALT n f g n g o 1P-LSD g , a l e l Alcoho v , GHB, GBL l c s n a p 25[-x]-NBOMe d b i i o c e w o r 5-MeO-DIBF , d k xide m n diazepo 25[- o x]-NBOH o , i s Chlor o n a Poppers
    [Show full text]
  • CREW NPS Booklet
    NEW Psychoactive DRUGS V1.7 05/15 Service availability Drop-in: Monday – Wednesday: 1pm – 5pm, Thursday: 3pm – 7pm, Friday – Saturday: 1pm – 5pm, Sunday: Closed Telephone information and support: Monday – Friday: 10am – 5pm Online information and chatroom support: www.mycrew.org.uk Address | 32 Cockburn Street | Edinburgh | EH1 1PB Telephone | 0131 220 3404 Email | [email protected] Main | www.crew2000.org.uk Enterprise | www.mindaltering.co.uk Info and support | www.mycrew.org.uk Facebook | www.facebook.com/Crew2000 Twitter | www.twitter.com/Crew_2000 Instagram | www.instagram.com/Crew_2000 This booklet has been designed to expand worker knowledge and confidence in the area of NPS. It is most useful when discussed as part of Crew’s NPS training. Crew was established in 1992, in response to the rapid expansion of recreational drug use. We provide up-to-date information on the drugs that people are taking so they can make informed decisions about their own health. This is achieved using a stepped care approach and through collaboration with volunteers, service users and professionals. Crew neither condemns nor condones drug use, but we believe there are ways to reduce harm to health. As a national agency, Crew is at the forefront of emerging drug trends and we engage at all levels including service development, practice and policy. Our services include: – Support line: non-judgmental drug and sexual health information and support. – Drop-in: drug and sexual health information, condoms (NHS c:card service) and DJ workshops. – Outreach services: we provide welfare at large events, such as clubs and festivals to educate revellers on partying safely.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2014/0144429 A1 Wensley Et Al
    US 2014O144429A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0144429 A1 Wensley et al. (43) Pub. Date: May 29, 2014 (54) METHODS AND DEVICES FOR COMPOUND (60) Provisional application No. 61/887,045, filed on Oct. DELIVERY 4, 2013, provisional application No. 61/831,992, filed on Jun. 6, 2013, provisional application No. 61/794, (71) Applicant: E-NICOTINE TECHNOLOGY, INC., 601, filed on Mar. 15, 2013, provisional application Draper, UT (US) No. 61/730,738, filed on Nov. 28, 2012. (72) Inventors: Martin Wensley, Los Gatos, CA (US); Publication Classification Michael Hufford, Chapel Hill, NC (US); Jeffrey Williams, Draper, UT (51) Int. Cl. (US); Peter Lloyd, Walnut Creek, CA A6M II/04 (2006.01) (US) (52) U.S. Cl. CPC ................................... A6M II/04 (2013.O1 (73) Assignee: E-NICOTINE TECHNOLOGY, INC., ( ) Draper, UT (US) USPC ..................................................... 128/200.14 (21) Appl. No.: 14/168,338 (57) ABSTRACT 1-1. Provided herein are methods, devices, systems, and computer (22) Filed: Jan. 30, 2014 readable medium for delivering one or more compounds to a O O Subject. Also described herein are methods, devices, systems, Related U.S. Application Data and computer readable medium for transitioning a Smoker to (63) Continuation of application No. PCT/US 13/72426, an electronic nicotine delivery device and for Smoking or filed on Nov. 27, 2013. nicotine cessation. Patent Application Publication May 29, 2014 Sheet 1 of 26 US 2014/O144429 A1 FIG. 2A 204 -1 2O6 Patent Application Publication May 29, 2014 Sheet 2 of 26 US 2014/O144429 A1 Area liquid is vaporized Electrical Connection Agent O s 2.
    [Show full text]
  • Analytical Reference Standards
    Cerilliant Quality ISO GUIDE 34 ISO/IEC 17025 ISO 90 01:2 00 8 GM P/ GL P Analytical Reference Standards 2 011 Analytical Reference Standards 20 811 PALOMA DRIVE, SUITE A, ROUND ROCK, TEXAS 78665, USA 11 PHONE 800/848-7837 | 512/238-9974 | FAX 800/654-1458 | 512/238-9129 | www.cerilliant.com company overview about cerilliant Cerilliant is an ISO Guide 34 and ISO 17025 accredited company dedicated to producing and providing high quality Certified Reference Standards and Certified Spiking SolutionsTM. We serve a diverse group of customers including private and public laboratories, research institutes, instrument manufacturers and pharmaceutical concerns – organizations that require materials of the highest quality, whether they’re conducing clinical or forensic testing, environmental analysis, pharmaceutical research, or developing new testing equipment. But we do more than just conduct science on their behalf. We make science smarter. Our team of experts includes numerous PhDs and advance-degreed specialists in science, manufacturing, and quality control, all of whom have a passion for the work they do, thrive in our collaborative atmosphere which values innovative thinking, and approach each day committed to delivering products and service second to none. At Cerilliant, we believe good chemistry is more than just a process in the lab. It’s also about creating partnerships that anticipate the needs of our clients and provide the catalyst for their success. to place an order or for customer service WEBSITE: www.cerilliant.com E-MAIL: [email protected] PHONE (8 A.M.–5 P.M. CT): 800/848-7837 | 512/238-9974 FAX: 800/654-1458 | 512/238-9129 ADDRESS: 811 PALOMA DRIVE, SUITE A ROUND ROCK, TEXAS 78665, USA © 2010 Cerilliant Corporation.
    [Show full text]
  • ATP, 489 Absolute Configuration Benzomotphans, 204 Levotphanol
    Index AIDA, 495 Affinity labeling, analogs of (Cont.) cAMP, 409, 489 motphine,448 ATP, 409, 489 naltrexone, 449 [3H] ATP, 489 norlevotphanol,449 Absolute configuration normetazocine, 181 benzomotphans, 204 norpethidine, 232 levotphanol, 115 oripavine, 453 methadone and analogs, 316 oxymotphone, 449 motphine, 86 K-Agonists, 179,405,434 phenoperidine, 234 Aid in Interactive Drug Analysis, 495 piperazine derivatives, 399 [L-Ala2] dermotphin, 363 prodines and analogs, 272 [D-Ala, D-Leu] enkephalin (DADL), 68, 344 sinomenine, 28, 115 [D-Ala2 , Bugs] enkephalinamide, 347, 447 viminol, 400 [D-Ala2, Met'] enkephalinamide, 337, 346, Ac 61-91,360 371,489 Acetylcholine, 5, 407 [D-Ala2]leu-enkephalin, 344, 346, 348 Acetylcholine analogs, 186, 191 [D-Ala2] met-enkephalin, 348 l-Acetylcodeine, 32 [D-Ala2] enkephalins, 347 Acetylmethadols (a and (3) Alfentanil, 296 maintenance of addicts by a-isomer, 304, 309 (±)-I1(3-Alkylbenzomotphans, 167, 170 metabolism, 309 11(3-Alkylbenzomotphans, 204 N-allyl and N-CPM analogs, 310, 431 7-Alkylisomotphinans, 146 stereochemistry, 323 N-Alkylnorketobemidones, 431 synthesis, 309 N-Alkylnorpethidines, 233 X-ray crystallography, 327 N-Allylnormetazocine, 420 6-Acetylmotphine, receptor binding, 27 N-Allylnormotphine, 405 Acetylnormethadol, 323 N-Allylnorpethidine, 233 8(3-Acyldihydrocodeinones, 52 3-Allylprodines (a and (3), 256 14-Acyl-4,5-epoxymotphinans, 58 'H-NMR and stereochemistry, 256 7-Acylhydromotphones, 128 X-ray crystallography, 256 Addiction, 4 N-Allylnormetazocine, 420 Adenylate cyclase, 6, 409, 413, 424,
    [Show full text]
  • List of Psychoactive Drug Spirits for MD A-Methylfentanyl, Abilify
    List of Psychoactive Drug Spirits for MD A-Methylfentanyl, Abilify, abnormal basal ganglia function, abuse of medicines, Aceperone, Acepromazine, Aceprometazine, Acetildenafil, Aceto phenazine, Acetoxy Dipt, Acetyl morphone, Acetyl propionyl morphine, Acetyl psilocin, Activation syndrome, acute anxiety, acute hypertension, acute panic attacks, Adderall, Addictions to drugs, Addictions to medicines, Addictions to substances, Adrenorphin, Adverse effects of psychoactive drugs, adverse reactions to medicines, aggression, aggressive, aggressiveness, agitated depression, Agitation and restlessness, Aildenafil, Akuammine, alcohol abuse, alcohol addiction, alcohol withdrawl, alcohol-related brain damage, alcohol- related liver damage, alcohol mix with medicines for adverse reaction, Alcoholism, Alfetamine, Alimemazine, Alizapride, Alkyl nitrites, allergic breathing reactions to meds, choking to anaphallectic shock, & death; allergic skin reactions to meds, rash, itchyness, hives, welts, etc, Alletorphine, Almorexant, Alnespirone, Alpha Ethyltryptamine, Alpha Neoendorphin, alterations in brain hormones, alterations in mental status, altered consciousness, altered mind, Altoqualine, Alvimopan, Ambien, Amidephrine, Amidorphin, Amiflamine, Amisulpride, Amphetamines, Amyl nitrite, Anafranil, Analeptic, Anastrozole, Anazocine, Anilopam, Antabuse, anti anxiety meds, anti dopaminergic activity, anti seizure meds, Anti convulsants, Anti depressants, Anti emetics, Anti histamines, anti manic meds, anti parkinsonics, Anti psychotics, Anxiety disorders,
    [Show full text]
  • Club Drugs Wheel (Display Poster Version 1.0.4 • 30/08/2020)
    Club Drugs Wheel (Display poster version 1.0.4 • 30/08/2020) eartbeat, sweating ng h , en aci well-bein erg R nce, g, eu y y fide pho Be ep Con ppetite, clen ria lo le ed a ched ng s y wer jaw Co in , tch Lo upils, paranoia s nn g e i d p , an S e , af , ng late xie e ct s hi Di ings, arousal, im ty xu io u rm at sw pote S al n, n , a re aty ood nc w a d e w b e M A e ea ro e e sw l R t, u s r a MP i e s fr p , w sk w s r , aine a t o ia a Heroin a - t r MDPV Khat o r l o a le s r d one f m , 4F-MPH t n o th Methadone o n i b h i Coc t e i , A d h r n d a s p w eh , e c il u , Bupr MDMA i i p n e e MD yd o c n n i p c v t g , Ethylphenidate r e i v u a n F enorphine Mephedr a l , e entanyl Amphetamine t r e , t n p e d PMMA i h i s o s n n Morphine Methamphetamine n e d d u e / a y y e e a p PMA, o n e t s n t n e Methylone v , d g d Dihydr ButyloneAPB e f d c , o u e fi n i r r g , h v n i r AI 5/6- o r n l t e ocodeine y e n Tr 2- c m g i s amadol Kr d r o e s t Ethylone, t 2-MPPP d i o atom 3-FPM AI r i y e n 5/6-MAPB o C d a o e r MD F o m O-desmethyltr Isotonitazene t s n e i C o one 4,4’-DMAR A o e v V edr 4-MT n O U-47700 2-methyl x S amadol L a Me APDI O p h 4-MPM 5- M o s -bucinnazine Nicotine V t Caeine p i t g s m e Diazepam o o r a e n Nortilidine I x] u c s i m i o 5-IA 2C[- o n e n t o t 2CI, i d c 2CE, i u e i d k T 2CB, t o emazepam n , d i a c m 5-MeO-DALT n f g n g o 1P-LSD g , a l e l Alcoho v , GHB, GBL l c s n a p 25[-x]-NBOMe d b i i o c e w o r 5-MeO-DIBF , d k xide m n diazepo 25[- o x]-NBOH o , i s Chlor o n a Poppers
    [Show full text]
  • Florencio Zaragoza Dörwald Lead Optimization for Medicinal Chemists
    Florencio Zaragoza Dorwald¨ Lead Optimization for Medicinal Chemists Related Titles Smith, D. A., Allerton, C., Kalgutkar, A. S., Curry, S. H., Whelpton, R. van de Waterbeemd, H., Walker, D. K. Drug Disposition and Pharmacokinetics and Metabolism Pharmacokinetics in Drug Design From Principles to Applications 2012 2011 ISBN: 978-3-527-32954-0 ISBN: 978-0-470-68446-7 Gad, S. C. (ed.) Rankovic, Z., Morphy, R. Development of Therapeutic Lead Generation Approaches Agents Handbook in Drug Discovery 2012 2010 ISBN: 978-0-471-21385-7 ISBN: 978-0-470-25761-6 Tsaioun, K., Kates, S. A. (eds.) Han, C., Davis, C. B., Wang, B. (eds.) ADMET for Medicinal Chemists Evaluation of Drug Candidates A Practical Guide for Preclinical Development 2011 Pharmacokinetics, Metabolism, ISBN: 978-0-470-48407-4 Pharmaceutics, and Toxicology 2010 ISBN: 978-0-470-04491-9 Sotriffer, C. (ed.) Virtual Screening Principles, Challenges, and Practical Faller, B., Urban, L. (eds.) Guidelines Hit and Lead Profiling 2011 Identification and Optimization ISBN: 978-3-527-32636-5 of Drug-like Molecules 2009 ISBN: 978-3-527-32331-9 Florencio Zaragoza Dorwald¨ Lead Optimization for Medicinal Chemists Pharmacokinetic Properties of Functional Groups and Organic Compounds The Author All books published by Wiley-VCH are carefully produced. Nevertheless, authors, Dr. Florencio Zaragoza D¨orwald editors, and publisher do not warrant the Lonza AG information contained in these books, Rottenstrasse 6 including this book, to be free of errors. 3930 Visp Readers are advised to keep in mind that Switzerland statements, data, illustrations, procedural details or other items may inadvertently be Cover illustration: inaccurate.
    [Show full text]
  • Bindex 877..922
    j877 Index a acetone Abrus precatorius L. (jequirity bean) 804 – BAT value 520, 853 absinth 516 – blood concentration 520 absorption spectrophotometry (AS) 652–656, – clinical interpretation 522 668–671 – headspace-GC 171, 173, 519 ACE (angiotensin converting enzyme) – medical assessment 520 inhibitors – toxicity 522 – GC-MS 161 acetonitrile acebutolol – headspace-GC 171, 173 – HPLC 457 – hepatotoxicity 749 acenocoumarol 303 – protein precipitation 119 – HPLC 305 acetorphine 867 acephate acetylcholinesterase (AChE) – ADI value 596 – BAT value 853 – MAK value 596 – determination 760 – TLC 594 – enzyme stability 763 aceprometazine – half-life of inhibited AChE 762 – TBPE test 179 – metabolite binding 702 acetaldehyde (ethanal) acetylcholinesterase (AChE) inhibitor – headspace-GC 171, 173 – BAT value 853 acetamidoflunitrazepam acetyldigoxin 336 – HPLC 355 – elimination half-life 841 acetaminophen, see also paracetamol – plasma/serum concentration 841 – antidote 857 acetylmethadol 867 – clinical interpretation 205 6-acetylmorphine – elimination half-life 204, 841 – elimination half-life 247 – extraction 190 – GC–MS 247 – GC 198 – pharmacokinetics 247 – GC–MS 109, 112, 116 N-acetylprocainamide – HPLC 109, 112, 116, 193 – clinical interpretation 281 – immunoassay 203 – elimination half-life 281 – intoxication 144 – immunoassay 781 – medical assessment 204 – medical assessment 281 – metabolism 206 – metabolism 281 – plasma/serum concentration 841 – serum concentration 281 – serum concentration 204 acetylsalicylic acid 209 – toxic hemorrhagic
    [Show full text]