WO2007062184A2 - Processes for reducing contaminating michael acceptor levels in oxycodone and other compositions - Google Patents

Processes for reducing contaminating michael acceptor levels in oxycodone and other compositions Download PDF

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Publication number
WO2007062184A2
WO2007062184A2 PCT/US2006/045316 US2006045316W WO2007062184A2 WO 2007062184 A2 WO2007062184 A2 WO 2007062184A2 US 2006045316 W US2006045316 W US 2006045316W WO 2007062184 A2 WO2007062184 A2 WO 2007062184A2
Authority
WO
WIPO (PCT)
Prior art keywords
thiol
composition
oxycodone
ppm
michael
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2006/045316
Other languages
English (en)
French (fr)
Other versions
WO2007062184A3 (en
Inventor
Jules A. Shafer
Vladislav V. Telyatnikov
Hao Wang
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Controlled Chemicals Inc
Original Assignee
Controlled Chemicals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Controlled Chemicals Inc filed Critical Controlled Chemicals Inc
Priority to AU2006318445A priority Critical patent/AU2006318445B2/en
Priority to EP06838339A priority patent/EP1971607A2/en
Priority to KR1020137031487A priority patent/KR101561760B1/ko
Priority to MX2008006710A priority patent/MX2008006710A/es
Priority to CN2006800494626A priority patent/CN101346384B/zh
Priority to JP2008542458A priority patent/JP5415075B2/ja
Priority to KR1020087015013A priority patent/KR101417135B1/ko
Priority to KR1020157007999A priority patent/KR20150041176A/ko
Priority to CA2630703A priority patent/CA2630703C/en
Publication of WO2007062184A2 publication Critical patent/WO2007062184A2/en
Publication of WO2007062184A3 publication Critical patent/WO2007062184A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L5/00—Preparation or treatment of foods or foodstuffs, in general; Food or foodstuffs obtained thereby; Materials therefor
    • A23L5/20—Removal of unwanted matter, e.g. deodorisation or detoxification
    • A23L5/27—Removal of unwanted matter, e.g. deodorisation or detoxification by chemical treatment, by adsorption or by absorption
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
    • C07D489/02—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
    • C07D489/06—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with a hetero atom directly attached in position 14
    • C07D489/08—Oxygen atom
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/62—Detectors specially adapted therefor
    • G01N30/74—Optical detectors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/02—Food
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/15—Medicinal preparations ; Physical properties thereof, e.g. dissolubility
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N2030/022—Column chromatography characterised by the kind of separation mechanism
    • G01N2030/027—Liquid chromatography

Definitions

  • the oxycodone precursor 14-hydroxycodeinone is a Michael acceptor that commonly contaminates oxycodone preparations.
  • the process of this invention for Michael acceptor removal is useful for removing 14-hydroxycodeinone from oxycodone. It involves treating oxycodone with a thiol so as to convert 14-hydroxycodeinone to a thiol-Michael adduct.
  • the reaction is carried out in water at a suitable pH. The pH is chosen so as to allow one to obtain both a reasonably concentrated homogenous solution of oxycodone and a reasonable rate of reaction consistent with the production of a competitively priced oxycodone processed product.
  • the oxycodone product of EXAMPLE 11 (0.5 g, 1.6 mmol) was dissolved in 0.2 N HCl (10 mL).
  • EDTA (0.005 g, 0.017 mmol) was added and the solution pH was raised to 6.0-6.2 with 1 M sodium carbonate with stirring to dissolve any precipitated oxycodone.
  • sodium thioglycolate (0.025 g, 0.22 mmol).
  • known amounts of 14-hydroxycodeinone were introduced prior to addition of sodium thioglycolate.
  • Plotted on the ordinate is the ratio of the area obtained for the peak corresponding to the thiol-Michael adduct 2-(oxycodone-8-sulfanyl)-acetic acid (14-HCA) and the weight of oxycodone (Oxy) analyzed (Area Units (AU)/ mg).
  • Plotted on the abscissa is the ratio of the weight of the 14-hydroxycodeinone (14-HC) spike and the weight of oxycodone analyzed (ppm).

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Food Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Nutrition Science (AREA)
  • Polymers & Plastics (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Emergency Medicine (AREA)
  • Biomedical Technology (AREA)
  • Pain & Pain Management (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Cleaning Or Drying Semiconductors (AREA)
  • Processing Of Solid Wastes (AREA)
PCT/US2006/045316 2005-11-22 2006-11-22 Processes for reducing contaminating michael acceptor levels in oxycodone and other compositions Ceased WO2007062184A2 (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
AU2006318445A AU2006318445B2 (en) 2005-11-22 2006-11-22 Processes for reducing contaminating michael acceptor levels in oxycodone and other compositions
EP06838339A EP1971607A2 (en) 2005-11-22 2006-11-22 Processes for reducing contaminating michael acceptor levels in oxycodone and other compositions
KR1020137031487A KR101561760B1 (ko) 2005-11-22 2006-11-22 옥시코돈 및 다른 조성물에서 오염물질인 마이클 수용체 수준을 감소시키는 방법
MX2008006710A MX2008006710A (es) 2005-11-22 2006-11-22 Procedimientos para reducir niveles de aceptor de michael contaminantes en oxicodona y otras composiciones.
CN2006800494626A CN101346384B (zh) 2005-11-22 2006-11-22 用于降低羟考酮和其它组分中杂质迈克尔受体水平的方法
JP2008542458A JP5415075B2 (ja) 2005-11-22 2006-11-22 オキシコドン及び他の組成物中の混入しているマイケル受容体レベルを低減させる方法
KR1020087015013A KR101417135B1 (ko) 2005-11-22 2006-11-22 옥시코돈 및 다른 조성물에서 오염물질인 마이클 수용체수준을 감소시키는 방법
KR1020157007999A KR20150041176A (ko) 2005-11-22 2006-11-22 옥시코돈 및 다른 조성물에서 오염물질인 마이클 수용체 수준을 감소시키는 방법
CA2630703A CA2630703C (en) 2005-11-22 2006-11-22 Processes for reducing contaminating michael acceptor levels in oxycodone and other compositions

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US73908705P 2005-11-22 2005-11-22
US60/739,087 2005-11-22

Publications (2)

Publication Number Publication Date
WO2007062184A2 true WO2007062184A2 (en) 2007-05-31
WO2007062184A3 WO2007062184A3 (en) 2007-07-26

Family

ID=38042645

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2006/045316 Ceased WO2007062184A2 (en) 2005-11-22 2006-11-22 Processes for reducing contaminating michael acceptor levels in oxycodone and other compositions

Country Status (8)

Country Link
US (4) US7875623B2 (https=)
EP (2) EP2402346A1 (https=)
JP (2) JP5415075B2 (https=)
KR (3) KR101561760B1 (https=)
CN (2) CN101346384B (https=)
CA (1) CA2630703C (https=)
MX (2) MX2008006710A (https=)
WO (1) WO2007062184A2 (https=)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2923484A1 (fr) * 2007-11-09 2009-05-15 Sanofi Aventis Sa Procede de preparation de composes morphiniques
JP2009528366A (ja) * 2006-03-02 2009-08-06 マリンクロッド・インコーポレイテッド 低レベルのアルファ，ベータ−不飽和ケトン化合物を伴うモルフィナン−６−オン生成物の製造方法
US7674798B2 (en) 2004-03-30 2010-03-09 Purdue Pharma L.P. Oxycodone hydrochloride having less than 25 ppm 14-hydroxycodeinone
US7875719B2 (en) 2006-12-04 2011-01-25 Cox D Phillip Process for reducing impurities in oxycodone base
US7906647B2 (en) 2006-12-04 2011-03-15 Noramco, Inc. Process for preparing oxycodone having reduced levels of 14-hydroxycodeinone
WO2012003468A1 (en) * 2010-07-02 2012-01-05 Johnson Matthey Public Limited Company Process for the synthesis and purification of oxycodone
US8916707B2 (en) 2012-08-03 2014-12-23 Johnson Matthey Public Limited Company Process

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3175780A1 (en) 2003-12-18 2017-06-07 Metronom Health, Inc. Implantable biosensor and methods of use thereof
CN101346384B (zh) 2005-11-22 2012-07-04 控制化学品公司 用于降低羟考酮和其它组分中杂质迈克尔受体水平的方法
US9062062B1 (en) 2013-12-18 2015-06-23 Cody Laboratories, Inc. Synthesis of oxycodone hydrochloride
US8846923B1 (en) 2013-12-18 2014-09-30 Cody Laboratories, Inc. Preparation of 14-hydroxycodeinone sulfate
US10227354B2 (en) 2013-12-18 2019-03-12 Cody Laboratories, Inc. Conversion of oxycodone base to oxycodone hydrochloride
CA2954600A1 (en) 2014-07-09 2016-01-14 Rhodes Technologies Reduction of alpha, beta-unsaturated ketone levels in morphinan derivative compositions
US10695000B2 (en) 2015-09-02 2020-06-30 Metronom Health, Inc. Systems and methods for continuous health monitoring using an opto-enzymatic analyte sensor
CN109725065A (zh) * 2017-10-31 2019-05-07 中国石油化工股份有限公司 一种轻质油中硫醇类化合物的分析方法
CN113237988B (zh) * 2021-04-30 2021-12-31 北京济圣康泰国际医药科技有限公司 一种羟考酮液体制剂中降解杂质羟醛二聚体含量的检测方法

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US6552170B1 (en) * 1990-04-06 2003-04-22 Amgen Inc. PEGylation reagents and compounds formed therewith
JP2001505558A (ja) 1996-11-15 2001-04-24 シンソーブ バイオテック，インコーポレイテッド 炭化水素ライブラリーのコンビナトリアル合成
US6177567B1 (en) * 1999-10-15 2001-01-23 Boehringer Ingelheim Chemicals, Inc. Method for preparing oxycodone
EP1456214A2 (en) * 2001-12-14 2004-09-15 Charterhouse Therapeutics Limited Improvements in pharmaceutical compositions
TWI365880B (en) * 2004-03-30 2012-06-11 Euro Celtique Sa Process for preparing oxycodone hydrochloride having less than 25 ppm 14-hydroxycodeinone and oxycodone hydrochloride composition,pharmaceutical dosage form,sustained release oeal dosage form and pharmaceutically acceptable package having less than 25 pp
CN101346384B (zh) * 2005-11-22 2012-07-04 控制化学品公司 用于降低羟考酮和其它组分中杂质迈克尔受体水平的方法
MX2008010921A (es) * 2006-03-02 2008-09-03 Mallinckrodt Inc Procesos para preparar productos de morfinan-6-ona con bajos niveles de compuestos de cetona alfa, beta-insaturados.
EP2322926A1 (en) 2009-11-11 2011-05-18 Zedira GmbH Stabilized open form transglutaminase as a diagnostic indicator for autoimmune diseases

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11236098B2 (en) 2004-03-30 2022-02-01 Purdue Pharma L.P. Process for preparing oxycodone hydrochloride having less than 25 ppm 14-hydroxycodeinone
US10696684B2 (en) 2004-03-30 2020-06-30 Purdue Pharma L.P. Process for preparing oxycodone hydrochloride having less than 25 PPM 14-hydroxycodeinone
US9073933B2 (en) 2004-03-30 2015-07-07 Purdue Pharma L.P. Oxycodone hydrochloride having less than 25 PPM 14-hydroxycodeinone
US7674798B2 (en) 2004-03-30 2010-03-09 Purdue Pharma L.P. Oxycodone hydrochloride having less than 25 ppm 14-hydroxycodeinone
US7674800B2 (en) 2004-03-30 2010-03-09 Purdue Pharma L.P. Oxycodone hydrochloride having less than 25 PPM 14-hydroxycodeinone
US7674799B2 (en) 2004-03-30 2010-03-09 Purdue Pharma L.P. Oxycodone hydrochloride having less than 25 ppm 14-hydroxycodeinone
US12060361B2 (en) 2004-03-30 2024-08-13 Purdue Pharma L.P. Process for preparing oxycodone hydrochloride having less than 25 ppm 14-hydroxycodeinone
US7683072B2 (en) 2004-03-30 2010-03-23 Purdue Pharma L.P. Oxycodone hydrochloride having less than 25 ppm 14-hydroxycodeinone
US8822687B2 (en) 2004-03-30 2014-09-02 Purdue Pharma L.P. 8a,14-dihydroxy-7,8-dihydrocodeinone
US11384091B2 (en) 2004-03-30 2022-07-12 Purdue Pharma L.P. Process for preparing oxycodone hydrochloride having less than 25 ppm 14-hydroxycodeinone
US10689389B2 (en) 2004-03-30 2020-06-23 Purdue Pharma L.P. Process for preparing oxycodone compositions
US10407434B2 (en) 2004-03-30 2019-09-10 Purdue Pharma L.P. Process for preparing oxycodone compositions
US10259819B2 (en) 2004-03-30 2019-04-16 Purdue Pharma L.P. Process for preparing oxycodone compositions
US9777011B2 (en) 2004-03-30 2017-10-03 Purdue Pharma L.P. Process for preparing oxycodone compositions
JP2009528366A (ja) * 2006-03-02 2009-08-06 マリンクロッド・インコーポレイテッド 低レベルのアルファ，ベータ−不飽和ケトン化合物を伴うモルフィナン−６−オン生成物の製造方法
JP2013173765A (ja) * 2006-03-02 2013-09-05 Mallinckrodt Llc 低レベルのアルファ，ベータ−不飽和ケトン化合物を伴うモルフィナン−６−オン生成物の製造方法
US7875719B2 (en) 2006-12-04 2011-01-25 Cox D Phillip Process for reducing impurities in oxycodone base
US8058439B2 (en) 2006-12-04 2011-11-15 Noramco, Inc. Process for preparing oxycodone having reduced levels of 14-hydroxycodeinone
US7906647B2 (en) 2006-12-04 2011-03-15 Noramco, Inc. Process for preparing oxycodone having reduced levels of 14-hydroxycodeinone
US8455509B2 (en) 2007-11-09 2013-06-04 Sanofi Method for the preparation of morphine compounds
EA017287B1 (ru) * 2007-11-09 2012-11-30 Санофи-Авентис Способ получения морфийных соединений
JP2011503040A (ja) * 2007-11-09 2011-01-27 サノフイ−アベンテイス モルヒネ化合物の調製方法
FR2923484A1 (fr) * 2007-11-09 2009-05-15 Sanofi Aventis Sa Procede de preparation de composes morphiniques
WO2009092912A1 (fr) * 2007-11-09 2009-07-30 Sanofi-Aventis Procede de preparation de composes morphiniques
US8703950B2 (en) 2010-07-02 2014-04-22 Johnson Matthey Public Limited Co. Low ABUK oxycodone, its salts and methods of making same
AU2011274361B2 (en) * 2010-07-02 2014-09-18 Macfarlan Smith Limited Process for the synthesis and purification of oxycodone
GB2495062A (en) * 2010-07-02 2013-03-27 Johnson Matthey Plc Process for the synthesis and purification of oxycodone
WO2012003468A1 (en) * 2010-07-02 2012-01-05 Johnson Matthey Public Limited Company Process for the synthesis and purification of oxycodone
US8916707B2 (en) 2012-08-03 2014-12-23 Johnson Matthey Public Limited Company Process

Also Published As

Publication number Publication date
CN101346384B (zh) 2012-07-04
MX345055B (es) 2017-01-13
JP2013079279A (ja) 2013-05-02
EP2402346A1 (en) 2012-01-04
US10201174B2 (en) 2019-02-12
CN102816167A (zh) 2012-12-12
CN102816167B (zh) 2016-01-06
JP5415075B2 (ja) 2014-02-12
CA2630703A1 (en) 2007-05-31
KR20150041176A (ko) 2015-04-15
US20070149559A1 (en) 2007-06-28
CA2630703C (en) 2014-05-20
US20170027199A1 (en) 2017-02-02
JP2009516750A (ja) 2009-04-23
US9034893B2 (en) 2015-05-19
US20150148537A1 (en) 2015-05-28
CN101346384A (zh) 2009-01-14
US7875623B2 (en) 2011-01-25
US20110136849A1 (en) 2011-06-09
KR101561760B1 (ko) 2015-10-20
US9403838B2 (en) 2016-08-02
KR20140002807A (ko) 2014-01-08
KR20080096750A (ko) 2008-11-03
AU2006318445A1 (en) 2007-05-31
KR101417135B1 (ko) 2014-07-08
MX2008006710A (es) 2008-12-16
WO2007062184A3 (en) 2007-07-26
EP1971607A2 (en) 2008-09-24
HK1179622A1 (zh) 2013-10-04

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