DOCSLIB.ORG

Recent Advances on Liquid Chromatographic and Mass Spectrometric Analysis of Selective Estrogen Receptor Modulators (Serms) in Biological Fluids

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Recent Advances on Liquid Chromatographic and Mass Spectrometric Analysis of Selective Estrogen Receptor Modulators (Serms) in Biological Fluids Send Orders for Reprints to [email protected] Current Chromatography, 2014, 1, 41-51 41 Recent Advances on Liquid Chromatographic and Mass Spectrometric Analysis of Selective Estrogen Receptor Modulators (SERMs) in Biological Fluids Konstantinos M. Kasiotis1,*, Evangelia N. Tzanetou2 and Serkos A. Haroutounian2 1Benaki Phytopathological Institute, Laboratory of Pesticides Toxicology, 8 St. Delta Street, Athens, Kifissia 14561, Greece; 2Chemistry Laboratory, Agricultural University of Athens, Iera odos 75, Athens 11855, Greece Abstract: Selective Estrogen Receptor Modulators (SERMs) comprise a class of therapeutic agents widely prescribed for the prevention and treatment of breast cancer, osteoporosis and postmenopausal symptoms. SERMs are exemplified by Tamoxifen (TAM), a molecule displaying pronounced activity that is mediated through its in vivo active metabolites (Z)- 4-hydroxytamoxifen and endoxifen. The extensive in vivo metabolism of SERMs along with their wide use as medica- tions, has led to the development of specific methods for the efficient separation and accurate identification of their parent molecules and metabolites in biological fluids. For this purpose, Liquid Chromatography (LC) is considered the most effi- cient separation technique, especially when combined with mass spectrometry in simple (LC-MS) and/or tandem mode (LC-MS/MS), constituting the cutting edge analytical approach in terms of selectivity and sensitivity. This review intends to account the major recent advances on the LC-MS determination of SERMs and metabolites in biological fluids, a sub- ject not reviewed to date with the exception of TAM which was extensively reviewed on 2010, consequencing the inclu- sion of only very recent reports on TAM assessments. Keywords: Bioanalysis, biological fluids, endoxifen, extraction, HPLC, LC-MS, LC-MS/MS, mass spectrometry, metabolites, MRM transitions, precipitation, raloxifene, SERMs, solid phase, tamoxifen. INTRODUCTION the need for accurate and sensitive analysis of TAM and its metabolites in human biological fluids. Notwithstanding, the Selective Estrogen Receptor Modulators (SERMs) en- increased risk of developing endometrial cancer upon long- compass a class of therapeutic agents extensively prescribed term administration of TAM in connection with other toxic- for the prevention and treatment of breast cancer, osteoporo- ity parameters, has directed scientists towards the exploita- sis and postmenopausal symptoms. Tamoxifen (TAM) (Fig. tion of novel SERMs. Thus, a second generation of SERMs - 1) constitutes the prototype of first generation SERMs, exemplified by raloxifene (RAL)- along with a third genera- which is prescribed for the treatment of primary and metas- tion was developed [1]. Moreover, various analytical meth- tatic breast cancers. TAM reduces the incidence of estrogen ods were also developed aiming to expand their detectability receptor positive breast cancers by about 60 to 70 % in and include the novel SERMs as well. The corresponding healthy high risk women [1]. Structurally, first generation analytical findings suggest the existence of an extensive SERMs are poly-aromatic compounds that contain phenolic metabolic pathway -as previously stated- with some metabo- moieties which are prone to oxidative metabolism. TAM is a lites being analogues of TAM [4]. prodrug that is converted into various metabolites with the P450 cytochrome enzymes playing key role in these Reversed Phase High Performance Liquid Chromatogra- transformations [2]. The most therapeutically active metabo- phy (RP-HPLC) is the most widely used technique, espe- lites of TAM are N-desmethyl-4-hydroxytamoxifen (en- cially for water-soluble molecules. Many researchers in- doxifen) and 4-hydroxytamoxifen (4-OH-TAM), which are volved in bioanalysis utilize this technique on daily basis to 30- to 100-fold more potent compared to TAM. The anti- perform a wide range of bioavailability and/or pharmacoki- estrogenic activities of endoxifen and 4-hydroxytamo-xifen netic studies. Additionally, RP-HPLC analysis is used as are similar although endoxifen is also a potent inhibitor of routine choice for the separation-identification of SERMs aromatase and is present at a higher steady state concentra- and their metabolites, while the unambiguous identification tion in patients than 4-hydroxytamoxifen [3]. provided by mass spectrometry has found merit in drugs and metabolites analysis in conjunction with liquid chromatogra- In addition, TAM was top-ranked among the adverse phy. Advances in the development of silica-based particles analytical findings within the hormone antagonists and have increased the separation efficiency of the HPLC analy- modulators banned substances in 2010. The latter augmented sis. The latest development refers to the application of Ultra HPLC (UHPLC) that uses narrow-bore columns packed with *Address correspondence to this author at the Benaki Phytopathological very small particles (below 2 m), which finds numerous Institute, Laboratory of Pesticides Toxicology, 8 St. Delta Street, Athens, applications in SERMs separations (described below) and a Kifissia 14561, Greece; Tel: 00302108180384; Fax: 00302108180223; plethora of other analytes in various matrices [5]. To increase E-mail: [email protected] 2213-2414/14 $58.00+.00 © 2014 Bentham Science Publishers 42 Current Chromatography, 2014, Vol. 1, No. 1 Kasiotis et al. N O H N N O O HO TAM 4-Hydroxy TAM N-desmethyl TAM H N O N N O O HO Cl Endoxifen Clomiphene I N Idoxifene O OH O N O Cl Toremifene Cl HO Ospemifene N Lasofoxifene O N N O O N OH HO O O OH Bazedoxifene S S OH HO Arzoxifene Raloxifene HO O N O Acolbifene Fig. (1). Structures of TAM, its major metabolites and other SERMs. Recent Advances on Liquid Chromatographic and Mass Spectrometric Analysis Current Chromatography, 2014, Vol. 1, No. 1 43 accuracy and sensitivity of analysis HPLC was coupled with to the surface via covalent bonds or other nonpolar packing mass spectrometry. The use of mass spectrometry especially materials. These beads are porous in order to raise their sur- in tandem mode (HPLC-MS/MS) turned out to be an impor- face area available for binding. The majority of reports on tant analytical tool in the study of the metabolic fate of drugs SERMs analyses utilize C18 columns and in less extent C8 and other xenobiotics in living systems [6]. columns. The HPLC analyses of SERMs are vastly described for TAM since this molecule constitutes the first SERM During 2010 an extensive review published by Teunissen et al. covered the majority of bio-analytical methods for the developed and displays a high medicinal impact as the most prescribed SERM. As the number of SERMs increased identification/determination of TAM and its Phase I metabo- newer SERMs entered the analytical chemistry portfolio. lites [7]. The analysis of SERMs and other pharmaceuticals in bio- Since then, a substantial number of TAM analyses have logical fluids such as blood, serum/plasma or urine usually been published, intriguing us to summarize the recent ad- involves a liquid-liquid extraction step [9] and/or solid phase vances in the field. Specifically, the review herein envisages extraction (SPE) step [10] as well as protein precipitation. covering all currently available HPLC-MS methods for the The latter accounts for many applications reviewed in this detection of SERMs in biological fluids. Selected reports on report [11]. In order to better understand the analyses of HPLC analyses are also addressed, only when emphasis on these molecules it is important to understand their chemical the detection of SERMs with mass spectrometry is not ex- profile. tensively given. SERMS CHEMICAL PROFILE AND MOBILE PHASE REVERSED PHASE CHROMATOGRAPHY AND pH SERMs ANALYSIS The basic nature of SERMs accounts for their increased RP chromatography is by far the method of choice in ionization and decreased lipophilicity under acidic condi- HPLC applications, accounting approximately for 60% of all tions. This explains the preference of researchers for acidic reported methods [8]. In most cases the mobile phase is a mobile phase conditions in order to enhance ionization and polar solvent system comprised by a) water with an optional therefore shorten analysis time. When the sample contains buffer, and b) a water-miscible organic solvent, such as ace- impurities the use of basic mobile phase facilitates the sepa- tonitrile (ACN) or methanol (MeOH). During a RP-HPLC ration of analytes, as was demonstrated in an HPLC method the partitioning of analytes occurs between the polar mobile developed for bazedoxifene acetate [12]. Considering the phase and a non-polar stationary phase (Fig. 2). The latter importance of TAM and the fact that it was the first SERM typically consists of non-polar chemically modified silica prescribed the disclosure of pertinent works begins with (spherical silica beads,1.8-5 micron), which usually consists TAM and its metabolites. of either linear octadecyl (C18) or octyl C8 groups bounded UHPLC SENSITIVE DETECTIONS OF TAM AND PHASE I METABOLITES O Tandem mass spectrometry was used by Dahmane et al. to identify TAM and its metabolites in breast cancer patients Si [11]. Their method refers to the use of low volume of plasma (100 L) which was purified by protein precipitation and evaporation. The samples obtained were reconstituted with a N N O solution of MeOH/20mM ammonium formate 1:1 (v/v) and O the pH was adjusted to 2.9 with the addition of formic acid. The separation was performed using an Acquity
Load more

Recommended publications
  • TE INI (19 ) United States (12 ) Patent Application Publication ( 10) Pub
    US 20200187851A1TE INI (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No .: US 2020/0187851 A1 Offenbacher et al. (43 ) Pub . Date : Jun . 18 , 2020 ( 54 ) PERIODONTAL DISEASE STRATIFICATION (52 ) U.S. CI. AND USES THEREOF CPC A61B 5/4552 (2013.01 ) ; G16H 20/10 ( 71) Applicant: The University of North Carolina at ( 2018.01) ; A61B 5/7275 ( 2013.01) ; A61B Chapel Hill , Chapel Hill , NC (US ) 5/7264 ( 2013.01 ) ( 72 ) Inventors: Steven Offenbacher, Chapel Hill , NC (US ) ; Thiago Morelli , Durham , NC ( 57 ) ABSTRACT (US ) ; Kevin Lee Moss, Graham , NC ( US ) ; James Douglas Beck , Chapel Described herein are methods of classifying periodontal Hill , NC (US ) patients and individual teeth . For example , disclosed is a method of diagnosing periodontal disease and / or risk of ( 21) Appl. No .: 16 /713,874 tooth loss in a subject that involves classifying teeth into one of 7 classes of periodontal disease. The method can include ( 22 ) Filed : Dec. 13 , 2019 the step of performing a dental examination on a patient and Related U.S. Application Data determining a periodontal profile class ( PPC ) . The method can further include the step of determining for each tooth a ( 60 ) Provisional application No.62 / 780,675 , filed on Dec. Tooth Profile Class ( TPC ) . The PPC and TPC can be used 17 , 2018 together to generate a composite risk score for an individual, which is referred to herein as the Index of Periodontal Risk Publication Classification ( IPR ) . In some embodiments , each stage of the disclosed (51 ) Int. Cl. PPC system is characterized by unique single nucleotide A61B 5/00 ( 2006.01 ) polymorphisms (SNPs ) associated with unique pathways , G16H 20/10 ( 2006.01 ) identifying unique druggable targets for each stage .
    [Show full text]
  • Cytoplasmic Localization of RXR Determines Outcome in Breast
    cancers Article Cytoplasmic Localization of RXRα Determines Outcome in Breast Cancer Alaleh Zati zehni 1,†, Falk Batz 1,†, Vincent Cavaillès 2 , Sophie Sixou 3,4, Till Kaltofen 1 , Simon Keckstein 1, Helene Hildegard Heidegger 1, Nina Ditsch 5, Sven Mahner 1, Udo Jeschke 1,5,* and Theresa Vilsmaier 1 1 Department of Obstetrics and Gynecology, University Hospital Munich LMU, 81377 Munich, Germany; [email protected] (A.Z.z.); [email protected] (F.B.); [email protected] (T.K.); [email protected] (S.K.); [email protected] (H.H.H.); [email protected] (S.M.); [email protected] (T.V.) 2 IRCM—Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université Montpellier, Parc Euromédecine, 208 rue des Apothicaires, CEDEX 5, F-34298 Montpellier, France; [email protected] 3 Faculté des Sciences Pharmaceutiques, Université Paul Sabatier Toulouse III, CEDEX 09, 31062 Toulouse, France; [email protected] 4 Cholesterol Metabolism and Therapeutic Innovations, Cancer Research Center of Toulouse (CRCT), UMR 1037, Université de Toulouse, CNRS, Inserm, UPS, 31037 Toulouse, France 5 Department of Obstetrics and Gynecology, University Hospital, 86156 Augsburg, Germany; [email protected] * Correspondence: [email protected]; Tel.: +49-8214-0016-5505 † These authors equally contributed to this work. Citation: Zati zehni, A.; Batz, F.; Cavaillès, V.; Sixou, S.; Kaltofen, T.; Simple Summary: Considering the immense development of today’s therapeutic approaches in on- Keckstein, S.; Heidegger, H.H.; Ditsch, cology towards customized therapy, this study aimed to assess the prognostic value of nuclear versus N.; Mahner, S.; Jeschke, U.; et al.
    [Show full text]
  • In Vitro and in Silico Analyses of the Inhibition of Human Aldehyde Oxidase By
    JPET Fast Forward. Published on July 9, 2019 as DOI: 10.1124/jpet.119.259267 This article has not been copyedited and formatted. The final version may differ from this version. JPET #259267 In Vitro and In Silico Analyses of the Inhibition of Human Aldehyde Oxidase by Bazedoxifene, Lasofoxifene, and Structural Analogues Shiyan Chen, Karl Austin-Muttitt, Linghua Harris Zhang, Jonathan G.L. Mullins, and Aik Jiang Lau Downloaded from Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore jpet.aspetjournals.org (S.C., A.J.L.); Institute of Life Science, Swansea University Medical School, United Kingdom (K.A-M, J.G.L.M.); NanoBioTec, LLC., Whippany, New Jersey, U.S.A. (L.H.Z.); at ASPET Journals on September 29, 2021 Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore (A.J.L.) 1 JPET Fast Forward. Published on July 9, 2019 as DOI: 10.1124/jpet.119.259267 This article has not been copyedited and formatted. The final version may differ from this version. JPET #259267 Running Title In Vitro and In Silico Analyses of AOX Inhibition by SERMs Corresponding author: Dr. Aik Jiang Lau Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543. Downloaded from Tel.: 65-6601 3470, Fax: 65-6779 1554; E-mail: [email protected] jpet.aspetjournals.org Number of text pages: 35 Number of tables: 4 Number of figures: 8 at ASPET Journals on September 29, 2021 Number of references 60 Number of words in Abstract (maximum
    [Show full text]
  • Pharmaceutical Appendix to the Tariff Schedule 2
    Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 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. ABACAVIR 136470-78-5 ACIDUM LIDADRONICUM 63132-38-7 ABAFUNGIN 129639-79-8 ACIDUM SALCAPROZICUM 183990-46-7 ABAMECTIN 65195-55-3 ACIDUM SALCLOBUZICUM 387825-03-8 ABANOQUIL 90402-40-7 ACIFRAN 72420-38-3 ABAPERIDONUM 183849-43-6 ACIPIMOX 51037-30-0 ABARELIX 183552-38-7 ACITAZANOLAST 114607-46-4 ABATACEPTUM 332348-12-6 ACITEMATE 101197-99-3 ABCIXIMAB 143653-53-6 ACITRETIN 55079-83-9 ABECARNIL 111841-85-1 ACIVICIN 42228-92-2 ABETIMUSUM 167362-48-3 ACLANTATE 39633-62-0 ABIRATERONE 154229-19-3 ACLARUBICIN 57576-44-0 ABITESARTAN 137882-98-5 ACLATONIUM NAPADISILATE 55077-30-0 ABLUKAST 96566-25-5 ACODAZOLE 79152-85-5 ABRINEURINUM 178535-93-8 ACOLBIFENUM 182167-02-8 ABUNIDAZOLE 91017-58-2 ACONIAZIDE 13410-86-1 ACADESINE 2627-69-2 ACOTIAMIDUM 185106-16-5 ACAMPROSATE 77337-76-9
    [Show full text]
  • Patent Application Publication ( 10 ) Pub . No . : US 2019 / 0192440 A1
    US 20190192440A1 (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 /0192440 A1 LI (43 ) Pub . Date : Jun . 27 , 2019 ( 54 ) ORAL DRUG DOSAGE FORM COMPRISING Publication Classification DRUG IN THE FORM OF NANOPARTICLES (51 ) Int . CI. A61K 9 / 20 (2006 .01 ) ( 71 ) Applicant: Triastek , Inc. , Nanjing ( CN ) A61K 9 /00 ( 2006 . 01) A61K 31/ 192 ( 2006 .01 ) (72 ) Inventor : Xiaoling LI , Dublin , CA (US ) A61K 9 / 24 ( 2006 .01 ) ( 52 ) U . S . CI. ( 21 ) Appl. No. : 16 /289 ,499 CPC . .. .. A61K 9 /2031 (2013 . 01 ) ; A61K 9 /0065 ( 22 ) Filed : Feb . 28 , 2019 (2013 .01 ) ; A61K 9 / 209 ( 2013 .01 ) ; A61K 9 /2027 ( 2013 .01 ) ; A61K 31/ 192 ( 2013. 01 ) ; Related U . S . Application Data A61K 9 /2072 ( 2013 .01 ) (63 ) Continuation of application No. 16 /028 ,305 , filed on Jul. 5 , 2018 , now Pat . No . 10 , 258 ,575 , which is a (57 ) ABSTRACT continuation of application No . 15 / 173 ,596 , filed on The present disclosure provides a stable solid pharmaceuti Jun . 3 , 2016 . cal dosage form for oral administration . The dosage form (60 ) Provisional application No . 62 /313 ,092 , filed on Mar. includes a substrate that forms at least one compartment and 24 , 2016 , provisional application No . 62 / 296 , 087 , a drug content loaded into the compartment. The dosage filed on Feb . 17 , 2016 , provisional application No . form is so designed that the active pharmaceutical ingredient 62 / 170, 645 , filed on Jun . 3 , 2015 . of the drug content is released in a controlled manner. Patent Application Publication Jun . 27 , 2019 Sheet 1 of 20 US 2019 /0192440 A1 FIG .
    [Show full text]
  • Treatment of Moderate to Severe Dyspareunia with Intravaginal Prasterone Therapy: a Review
    Climacteric ISSN: 1369-7137 (Print) 1473-0804 (Online) Journal homepage: https://www.tandfonline.com/loi/icmt20 Treatment of moderate to severe dyspareunia with intravaginal prasterone therapy: a review D. J. Portman, S. R. Goldstein & R. Kagan To cite this article: D. J. Portman, S. R. Goldstein & R. Kagan (2019) Treatment of moderate to severe dyspareunia with intravaginal prasterone therapy: a review, Climacteric, 22:1, 65-72, DOI: 10.1080/13697137.2018.1535583 To link to this article: https://doi.org/10.1080/13697137.2018.1535583 © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group View supplementary material Published online: 17 Dec 2018. Submit your article to this journal Article views: 575 View Crossmark data Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=icmt20 CLIMACTERIC 2019, VOL. 22, NO. 1, 65–72 https://doi.org/10.1080/13697137.2018.1535583 REVIEW Treatment of moderate to severe dyspareunia with intravaginal prasterone therapy: a review D. J. Portmana,b, S. R. Goldsteinc and R. Kagand,e aColumbus Center for Women’s Health Research, Columbus, OH, USA; bSermonix Pharmaceuticals, Columbus, OH, USA; cDepartment of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA; dDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA, USA; eSutter East Bay Medical Foundation, Berkeley, CA, USA ABSTRACT ARTICLE HISTORY The loss of sex steroids (e.g. estradiol, dehydroepiandrosterone [DHEA], progesterone) that causes Received 11 May 2018 menopause commonly affects a woman’s general health and produces bothersome physical changes Revised 25 September 2018 that may interfere with normal sexual and genitourinary functioning.
    [Show full text]
  • Lääkeaineiden Yleisnimet (INN-Nimet) 21.6.2021
    Lääkealan turvallisuus- ja kehittämiskeskus Säkerhets- och utvecklingscentret för läkemedelsområdet Finnish Medicines Agency Lääkeaineiden yleisnimet (INN-nimet) 21.6.
    [Show full text]
  • Nontargeted Discovery of Xenobiotics in Human Urine by Maldi-Tof/Tof-Ms
    NONTARGETED DISCOVERY OF XENOBIOTICS IN HUMAN URINE BY MALDI-TOF/TOF-MS Dissertation Presented by Yuanyuan Yao To The Bouve’ Graduate School of Health Sciences in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Pharmaceutical Sciences with specialization in Biomedical Sciences NORTHEASTERN UNIVERSITY BOSTON, MASSACHUSETTS April 2018 ABSTRACT In this dissertation research, nontargeted analysis of the urine metabolome, including xenobiotics, was studied using LC (Liquid Chromatography)-MALDI (Matrix Assisted Laser Desorption Ionization) MS (Mass Spectrometry) techniques. MALDI is a sensitive soft ionization MS technique that has been mainly used to analyze large molecules such as peptides, proteins, and nucleic acids. Here, MALDI MS methods were employed for detection of urine metabolites. To increase the recovery of nonpolar metabolites, a novel porous extraction paddle (PEP) was validated with co-workers and used for urine extraction. A method for sample preparation including UHPLC (Ultra High-Performance Liquid Chromatography) was optimized to facilitate detection of nonpolar urine sulfate metabolites by MALDI MS. Using this approach, the detection coverage of such compounds was greatly expanded as compared to prior methods. Detection of 1129 MS precursor ions corresponding to putative sulfate and glucuronide metabolites was achieved. Combining MS and MS/MS experiments, a strategy was developed for tentative identification of the detected metabolites. This led to the first nontargeted analysis of environmental contaminants in urine. It was shown that the detection sensitivity of positive-mode MALDI MS can be enhanced using enzymatic deconjugation and cationic tagging methods. Also, an evaporative derivatization method was developed to increase the sensitivity of negative-mode MALDI MS for detection of phenolic compounds.
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2001/0047033 A1 Taylor Et Al
    US 20010047033A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2001/0047033 A1 Taylor et al. (43) Pub. Date: Nov. 29, 2001 (54) COMPOSITION FOR AND METHOD OF Publication Classification PREVENTING OR TREATING BREAST CANCER (51) Int. Cl." ........................ A61K 31/35; A61K 31/138 (52) U.S. Cl. ............................................ 514/456; 514/651 (75) Inventors: Richard B. Taylor, Valley Park, MO (US); Edna C. Henley, Athens, GA (57) ABSTRACT (US) The present invention is a composition for preventing, Correspondence Address: minimizing, or reversing the development or growth of Richard B. Taylor breast cancer. The composition contains a combination of a Protein Technologies International, Inc. Selective estrogen receptor modulator Selected from at least P.O. BOX 88940 one of raloxifene, droloxifene, toremifene, 4'-iodotamox St. Louis, MO 63188 (US) ifen, and idoxifene and at least one isoflavone Selected from genistein, daidzein, biochanin A, formononetin, and their (73) Assignee: Protein Technologies International, respective naturally occurring glucosides and glucoside con Inc., St. Louis, MO jugates. The present invention also provides a method of (21) Appl. No.: 09/900,573 preventing, minimizing, or reversing the development or growth of breast cancer in which a Selective estrogen (22) Filed: Jul. 6, 2001 receptor modulator Selected from at least one of raloxifene, droloxifene, toremifene, 4'-iodotamoxifen, and idoxifene is Related U.S. Application Data co-administered with at least one isoflavone Selected from genistein, daidzein, biochanin A, formononetin, and their (62) Division of application No. 09/294,519, filed on Apr. naturally occuring glucosides and glucoside conjugates to a 20, 1999. woman having or predisposed to having breast cancer.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,158,152 B2 Palepu (45) Date of Patent: Apr
    US008158152B2 (12) United States Patent (10) Patent No.: US 8,158,152 B2 Palepu (45) Date of Patent: Apr. 17, 2012 (54) LYOPHILIZATION PROCESS AND 6,884,422 B1 4/2005 Liu et al. PRODUCTS OBTANED THEREBY 6,900, 184 B2 5/2005 Cohen et al. 2002fOO 10357 A1 1/2002 Stogniew etal. 2002/009 1270 A1 7, 2002 Wu et al. (75) Inventor: Nageswara R. Palepu. Mill Creek, WA 2002/0143038 A1 10/2002 Bandyopadhyay et al. (US) 2002fO155097 A1 10, 2002 Te 2003, OO68416 A1 4/2003 Burgess et al. 2003/0077321 A1 4/2003 Kiel et al. (73) Assignee: SciDose LLC, Amherst, MA (US) 2003, OO82236 A1 5/2003 Mathiowitz et al. 2003/0096378 A1 5/2003 Qiu et al. (*) Notice: Subject to any disclaimer, the term of this 2003/OO96797 A1 5/2003 Stogniew et al. patent is extended or adjusted under 35 2003.01.1331.6 A1 6/2003 Kaisheva et al. U.S.C. 154(b) by 1560 days. 2003. O191157 A1 10, 2003 Doen 2003/0202978 A1 10, 2003 Maa et al. 2003/0211042 A1 11/2003 Evans (21) Appl. No.: 11/282,507 2003/0229027 A1 12/2003 Eissens et al. 2004.0005351 A1 1/2004 Kwon (22) Filed: Nov. 18, 2005 2004/0042971 A1 3/2004 Truong-Le et al. 2004/0042972 A1 3/2004 Truong-Le et al. (65) Prior Publication Data 2004.0043042 A1 3/2004 Johnson et al. 2004/OO57927 A1 3/2004 Warne et al. US 2007/O116729 A1 May 24, 2007 2004, OO63792 A1 4/2004 Khera et al.
    [Show full text]
  • Selective Estrogen Receptor Modulator BC-1 Activates Antioxidant Signaling Pathway in Vitro Via Formation of Reactive Metabolites
    Acta Pharmacologica Sinica (2013) 34: 373–379 npg © 2013 CPS and SIMM All rights reserved 1671-4083/13 $32.00 www.nature.com/aps Original Article Selective estrogen receptor modulator BC-1 activates antioxidant signaling pathway in vitro via formation of reactive metabolites Bo-lan YU1, *, Zi-xin MAI1, Xu-xiang LIU2, Zhao-feng HUANG2, * 1Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institute, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China; 2Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Aim: Benzothiophene compounds are selective estrogen receptor modulators (SERMs), which are recently found to activate antioxidant signaling. In this study the molecular mechanisms of antioxidant signaling activation by benzothiophene compound BC-1 were investigated. Methods: HepG2 cells were stably transfected with antioxidant response element (ARE)-luciferase reporter (HepG2-ARE cells). The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in HepG2-ARE cells was suppressed using siRNA. The metabolites of BC-1 in rat liver microsome incubation were analyzed using LC-UV and LC-MS. Results: Addition of BC-1 (5 μmol/L) in HepG2-ARE cells resulted in a 17-fold increase of ARE-luciferase activity. Pretreatment with the estrogen receptor agonist E2 (5 μmol/L) or antagonist ICI 182,780 (5 μmol/L) did not affect BC-1-induced ARE-luciferase activity. However, transfection of the cells with anti-Nrf2 siRNA suppressed this effect by 79%. Addition of BC-1 in rat microsome incubation resulted in formation of di-quinone methides and o-quinones, followed by formation of GSH conjugates.
    [Show full text]