Pract· al
`High- erformance
`·quid
`
`ato raphy
`
`Veronika R. Meyer
`
`LOWER DRUG PRICES FOR CONSUMERS, LLC
`Exhibit 1011-1
`IPR2016-00379
`
`

`
`LOWER DRUG PRICES FOR CONSUMERS, LLC
`Exhibit 1011-2
`IPR2016-00379
`
`

`
`Copyright© 1988 by John Wiley & Sons Ltd.
`© 1979 Verlag Moritz Diesterweg GmbH & Co., Otto Salle Verlag
`GmbH & Co., Frankfurt a. Main, Verlag Sauerlander AG, Aarau /5.
`vollstandig iiberarbeitete Auflage 1988.
`
`All rights reserved.
`
`No part of this book may be reproduced by any mea ns, or transmitted, or
`translated into machine language without the written permission of the publisher.
`
`Library of Congress Cataloging in Publication Data:
`Meyer, Veronika.
`[Praxis der Hochleistungs-Fliissigchromatographie. English]
`Practical high performance liquid chromatography I Veronika R. Meyer.
`cm.
`p.
`Translation of: Praxis der Hochleistungs-Fliissigchromatographie .
`Includes indexes.
`ISBN 0 471 91140 2 (U.S.):
`1. High performance liquid chromatography.
`QD79.C454M4913 1988
`543' .0894--dc19
`
`I. Title.
`
`British Library Cataloguing in Publication Data:
`Meyer, Veronika R.
`Practical high performance liquid
`chromatography.
`1. High performance liquid chromotography
`L Title
`543' .0894
`
`QD79.C454
`
`ISBN 0 471 91140 2
`Typeset by Photo-graphics, Honiton , Devon
`Printed by Biddies Ltd., Guildford, Surrey
`
`LOWER DRUG PRICES FOR CONSUMERS, LLC
`Exhibit 1011-3
`IPR2016-00379
`
`

`
`Contents
`
`Preface ............................................................. ....................................... xiii
`
`1 Introduction . . . . .. . . .. . . . . .. . . . . .. . . . .. . .. . . . . .. .. .. . . .. .. .. . . . . ... . . . .. .. .. .. ..........
`1.1 What is HPLC? ..............................................................
`1.2 Comparison between high-performance liquid chroma-
`tography and gas chromatography ............................... .
`1.3 Liquid chromatography separation modes .. ..................
`1.4 Apparatus for HPLC .................. .... .................................
`1.5 Safety in the HPLC area .. .. .. . . . . .. .. . . . . . . .. .. .. . . . . . ... .. . . . ..... .. .
`1.6 Pressure units .. .. . . . . .. . .. . . . . . . . . . .. .. . .. .. . .. .. . . . .. .. . .. .. .. . .. . . . .. . . .. . .
`1.7 Length units ..................................... ..... ..........................
`1.8 Bibliography on HPLC .......................... ...... .................. ..
`
`2 Theoretical principles .. .. . . .. . . . . . .. . .. . .. . . . .. .. . . . .. .. . . . .. . . . .. ... .. . . .. . . . . ..
`2.1 The chromatographic process . . .. . . .. .. . . . .. . ... ... .. . .. .. .. . .. .. . . .
`2.2 - Band broadening .. .. . .. .. . .. . . . . .. . . .. . . . . . . .. .. . . . .. . . . . . .. .. . .. . . . .. .. .. . .
`2.3 The chromatogram and its uses .. .. . .. .. . .. .. . . . . . . . .. . .. .. . . . .. . . .
`2.4 Factors affecting resolution ............................................
`2.5 Extra-column volumes (dead volumes) .........................
`2.6 Tailing .... ...... ...... ................. ........................ ....................
`2.7 Peak capacity ...................................... ...........................
`2.8 Effect of temperature in HPLC . .. .. . . . .. . . . . . .. .. . . . .. . . . . . .. . . . .. . .
`2.9 Limits of HPLC ...............................................................
`
`3 Pumps ......................................................................................
`3.1 Gas-driven discontinuous displacement systems . . . . .. . . ..
`3.2 Discontinuous displacement pumps . .. .. . .. .. . . . . . . . .. . . . .. . . . . . .
`3.3 Membrane pumps (membrane piston pumps) ..............
`3.4 Short-stroke piston pumps .............................................
`3.5 Pneumatic amplifier pumps . . ... . .. .. . . . .. . .. .. . .. . . . . . .. .. .. .. . . .. .. ..
`
`Vil
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`LOWER DRUG PRICES FOR CONSUMERS, LLC
`Exhibit 1011-4
`IPR2016-00379
`
`

`
`viii
`
`4 Preparation of equipment up to sample injection . . .. . . . . .. ..
`4.1 Selection of mobile phase . ... .. .. .. . .. ... . .. . .. .. . . .. . . . . . . .. .. .. . . .. .
`4.2 Preparation of mobile phase ..........................................
`4.3 Gradient systems ... .. ... .. . ... .. .. ... . .... .... .. .. ... ........ ... . .. .. .. . .. .
`4.4 Tubing, manometers and pulse dampers .. .. .... .. .. .. .. ... .. .
`4.5 Sample injectors .. ..... .... .. .. .... ......... ... ......... ... ... .. . . .. ... ... ...
`4.6 Sample solution and sample volume ..... . .. .. ..................
`
`5 Detectors . . . . .. . . . . .. . . .. .. . . .. .. . .. . . . .. . . . . .. . . .. . . .. .. . . . . .. .. . . . . .. .. . . .. . .. . . . .. . . . . .
`5.1 General . .. ..... .. .. .... .. . . .. .. .. .. .. . .. .. .. . .. ... ... .. .. . . .. .. .. .. .. . .. ... .. .. .. .
`5.2 UV detectors .. .. .... .. ... ..... . ...... .. .. . .. .. . .. . .. ...... .. .... .. . .. . .. . ... . . .
`5.3 Refractive index detectors ... .. ..... .. . ..... .. .. .. ... .... .. ... .. . .... ..
`5.4 Fluorescence detectors .. .... .. .......... ..... ... ... .. ... .. .. ... .. ... .. ..
`5.5 Electrochemical (amperometric) detectors ....................
`5.6 Other detectors ...............................................................
`5. 7 Multiple detection . ... .. .. .. .. ....... ... ........ ..... ......... ...... ... .... . .
`5.8
`Indirect detection .. .. ... ... ... . .. .... .. ..... ... .. ... ... .. .... .. .... .. . .......
`
`6 Columns and stationary phases . ........... .... .... .. .. ... ............ ...
`6.1 Columns for HPLC .. .. .. .... .. .. .... . .... .... .... ... .. .. . . ....... .. . .......
`6.2 Pre-columns ........................................... .........................
`6.3 General information on column packings ......................
`6.4 Silica gel .............................................. ............ .............. .
`6.5 Chemically modified silica gel .. .... .... .... ....... .... ... ...... ... .. .
`6.6 Styrene-divinylbenzene ...... ..... .. .... .. ... .. .. .......... ... ... ... . .. . .
`6. 7 Some other stationary phases ............. ...... . .. .. .. .. .. .........
`
`7 Column packing and regeneration ... .. ... .. .. . . .. .. .. .. ........ ... .. ...
`7.1 Packing ...........................................................................
`7.2 Column regeneration ......................................................
`7.3 Column emptying ...........................................................
`
`8 HPLC column tests ................. ...............................................
`8.1 Simple tests for HPLC columns . ................. ...... .. .. ........
`8.2 Determination of particle size .. .... ......... ... ... .. . .. .. .. . .. .... ...
`8.3 Determination of breakthrough time . ... . .. ... ....... .. . ... .. . .. . .
`8.4 The test mixture . . . . .. .. . ....... .. .. .... .. .. .. . ........ ................. ... . .
`8.5 Dimensionless values for HPLC column characterization
`8.6 Van Deemter equation from reduced values and its use
`in column diagnosis .. ... .... .. ... .... ... ... .. .. .. .. . .. .. . .. .. .. .. . ... . ... .
`8. 7 Calculation of diffusion coefficients . .. .... .. ... ... .... . .. .. . .. .. ..
`8.8 Appendix: Diffusion coefficients of macromolecules . ... .
`
`9 Adsorption chromatography .. . . . . .. .. . .. . . . .. .. . .. .. . .. .. .. . . .. . . . . .. . . .. . ..
`9 .1 What is adsorption ? .. .. .. .. . .. . .. . .. . . .. . . .. .. . . .. . . .. .. .. . . .. .. .. .. . .. .. .
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`LOWER DRUG PRICES FOR CONSUMERS, LLC
`Exhibit 1011-5
`IPR2016-00379
`
`

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`- ·-------------------------·
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`-
`
`9.2 The eluotropic series ... ..... .......... ............. ..... .... ......... .....
`9.3 Choice of mobile phase .................................................
`9.4 - Optimization of mobile phase ........................................
`9.5 Use of deactivators . . ... . . .. . .. .. . . .... . .... ... .. .. . .. .... . .... ......... ...
`9.6 Change of mobile phase ....... .........................................
`9.7 Applications ....................................................................
`
`1 O Reversed-phase chromatography .. ... . . . .. .. . ... ..... . .. ... . .. ...... ....
`10.1 Principle . . .. .. . . .. . . . . .. . . . . .. ... . ..... . . . .. .. ... .. . .. .. .. .. . ..... .. .. .. .... . . . . ..
`10.2 Mobile phases in reversed-phase chromatography .. ... .
`10.3 Special selectivity effects from ternary solvent mixtures
`10.4 Selectivity triangle in reversed-phase chromatography
`10.5 Stationary phases .. .. .. .. .... .. . ....... ... .... ..... .. .. .... .. .... ...... .. .. .
`10.6 Applications . .. ... . . . . .. . .. . .. . . . .. . .. .. .... .. .... . . .. ... .. ... . .. .. . . ..... .. ....
`10. 7 Hydrophobic interaction chromatography . . .. .. .. .. .. .. .. . . . .. .
`
`11 Liquid-liquid partition chromatography .............. ................
`11.1 Principle .. .. .. .. .. .. .. .. .. .. .. .. . . . .. . .. .. . .. . . .... . .. . . ..... . .. . . . ... . . .... .. . . . .
`11 .2 Phase systems . . . . . . . . . . . . . . . . . .. . . . . . . .. .. .. .. . . .. .. .. .. . .. .. .. .. .. .. .. . . . . .
`11.3 Support materials .... .. .. .... .. .. . .. . .... . .. .. . . . .. . . . . ... .. . .. .. . . . . ... ... .
`11 .4 Column preparation .. .. .. . .. ... .. . . . . . . .. . . . . . .. . .. .. .. .. . . . .. .. ...........
`11.5 Liquid-liquid partition chromatography in practice .. . .. ...
`11.6 Applications .... .. ........ .. .. ... .. . . . .. . .. . .. .. ..... ....... ......... ... .. .. . .. .
`
`12 Chromatography with chemically bonded phases............
`12.1
`Introduction .... ............ ..... ........ ..... .. ................. ................
`12.2 Properties of some stationary phases .... ~.. .. .................
`12.3 Prospects .. . .. .. .... .. . .. .. . . .. .. . ... .. .. .. ... . . ... .. ... ... .. .. .. .. .... .. .. .. ....
`
`13 Ion-exchange chromatography ... .. . . .... .. . . . . . .. .. . . . .. .. .. .. ..... .. . . . .
`13.1 Introduction .. .. .. .. ... . .. .. . .. ... . .. .. . . . ...... ...... ... . . ... . .... .... .... .. . . . .
`13.2 Principle .. . .. .. . .. . . .. .. .. .. ... . . .. . .... .. . .. ... .. ...... ... . . . .. ...... .. .. .. .. . . . .
`13.3 Types of ion exchanger . . .. .. .. . .... .. .. . .. . .. . .. .. .... . .. .. ... .. .. .. . ..
`13.4 Influence of the mobile phase .......................................
`13.5 Special possibilities of ion exchange .. . . . . . . .. .. . .. .. .. . .. .. .. . ..
`13.6 Practical hints ...................... ...................... .....................
`13.7 Applications ....................................................................
`
`14 Ion-pair chromatography ......................................................
`14.1 Introduction .. . ...... .. ... . .. .. .... . . .. .. . .. . .. .... . .. .. . . . . . . . .. . .. .. .. . . ... . ...
`14.2 Ion-pair chromatography in practice ... .. . . . . .. . .. . .. .. . .. .... .. ..
`14.3 Applications .. .. .. ... .. .. . ... . . . .. .. . ... . .. . .. .. ... .. ... .. . .. .. . .... .. . .. ... . . ..
`14.4 Appendix: UV detection using ion-pair reagents . ... .. .. . ..
`
`IX
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`LOWER DRUG PRICES FOR CONSUMERS, LLC
`Exhibit 1011-6
`IPR2016-00379
`
`

`
`x
`
`15 Ion chromatography . . .. . . . .. . . . . . .. . . . . .. .. . . . . .. . . . . . ... . . . . .. . . .. .. . . .. .. . .. . ..
`15.1
`Introduction .. . . . . . . . . . . .. . . .. . . . . .. .. . . . . . . . . . . . . .. .. . .. . .. . . . . .. . . . . . . . .. . .. . ..
`15.2
`Ion chromatography in practice ............ ...... ...... ...... .......
`15 .3 Conductivity detection with chemical suppression (dual-
`column ion chromatography) .. . . . . . . .. .. .. . . .. . .. . .. . . . . .. .. . . .. .. . . .
`15.4 Conductivity detection with electronic suppression (sin-
`gle-column ion chromatography) . . .. . . .. . .. . . . .. . . . .. . . . . . . . . . .. ...
`Indirect UV detection .. .. .. .. . . . ..... .. . . .. . . .. . . . . . . ........ .. . . . . .. . . .. ..
`
`15.5
`
`16 Size-exclusion chromatography . . .. . ... .. . . . . . . .. . . . . .. . . . . .. . . .. . . . . . . . . .
`16.1 Principle . . . . . . . . .. . . . . . .. .. ... . . . . . . .. .. . .. .. . . . .. . . .. . . . . . . .. . . .. . . . . . . . . . . .. . . . .
`16.2 The calibration chromatogram . . . .. . . ... . . . . .. . . . . .. . . . . . . . . . . . . . . . . .
`16.3 Molecular mass determination by means of size-
`exclusion chromatography .. . . . . . . .. . . . . . . . . . . . . . . .. . . . . . . . . .. . ... .. .. .
`16.4 Coupled size-exclusion columns . .. . .. .. . . . . . . . . .. . .. . . . . . . . .. . .. . . .
`16.5 Phase systems . . .. . . . . . . . . . . . . .. . . . .. . . . .. . . . . .. . ... .. .. . . .. . . .. .. . . . . ... . . ..
`16.6 Applications ....................................................................
`
`17 Affinity chromatography . . . . ...... .. . . .. .. . . .. .. .. .. .. . . .. .... ... . .. .. . . . . . . . . ..
`17.1 Principle ....... ... ...... ... ........................... ...... .... ....... ....... ....
`17.2 Affinity chromatography as a special case of HPLC ....
`17.3 Applications ...................... ...... .. .... .. .... .... .. ........ .... .. .... ....
`
`18 Choice of method . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`19 Solving the elution problem . . . . .. . . . . . . . . . . . . . .. . . .. . .. .. . .. . . . . . . .. . .. .. .. .
`19.1 The elution problem ................. ....... ...............................
`19.2 Solvent gradients ............................ .............. .......... ........
`19.3 Column coupling ... . .. . . . . . ... ........ ... . ...... .. . . . . . . .. . . .. .. . . .. . . . . . . . . .
`19.4 Optimization of an isocratic chromatogram using four
`solvents . ..... .. . .. . . . .... .. .. .. ... . . .. .. ... .. .. . . . . .. . . . . . . . . . . . . . . . . . . . . . . .. . .. . .
`19.5 Optimization of other parameters . . . . . . .. .. . . .. . . . . . . . . . . . . . . .. .. . .
`19.6 Mixed stationary phases .......................................... ......
`
`20 Analytical HPLC .. ...... ...... ........... ..... ..... ........... ...... ....... ..........
`20.1 Qualitative analysis .......... .......... .. .................... ..............
`20.2 Trace analysis ...... ...... .......... ....................... ...................
`20.3 Quantitative analysis ............ ...................... ....................
`20.4 Peak-height and peak-area measurement for quantitative
`analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`20.5 Derivatization ..................................................................
`20.6 Special detection possibilities ........................................
`20.7 Unexpected peaks: ghost and system peaks ...............
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`LOWER DRUG PRICES FOR CONSUMERS, LLC
`Exhibit 1011-7
`IPR2016-00379
`
`

`
`21 Preparative HPLC .. .. . . . .. .. . .. . ... . . .. .. . .. ... .. ... . .. .. .. .. .. .. . . . .. ... .. .. .. . .. .
`21.1 Problem ..........................................................................
`21.2 Preparative HPLC in practice ........................................
`21 .3 Overloading effects ................ ........................................
`21.4 Sampling ............. ...................................... ................... ...
`21 .5 Recycling . . . .. . . . . . .. .. . . .. ... .. .. . . . . . . . . . .. .. .. ... .. ... . . . . .. . . . .. . . .. . .. .. . . ..
`21.6 Displacement chromatography ............ ..... ............. ...... ...
`
`22 Separation of enantiomers . . .. .. . . . .. .. .. .. .. .. . .. .. . .. .. . . .. . . .. . . . . .. . .. .. .
`22.1
`Introduction .... .................... ..... ..... .............. ..... .... ..... ..... ..
`22.2 Chiral mobile phases .. .. . . .. . . .. . . . . . . . . .. .. . .. . . . . . . . .. . .. .. .. . .. .. .. . . .
`22.3 Chiral liquid stationary phases ...... .............. ..... .... ..... .....
`22.4 Chiral solid stationary phases .. .. .. .. .. .. .. .... . . . .. ..... ... . . .. .. . ..
`
`23 New prospects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`23.1 Micro and capillary HPLC . ... .. .. . .... .... . .. .. . . . .. .. . .. .... .. . .. .. ...
`23.2 High-speed and super-speed HPLC . . . . . . . .. .. . . . . ... . . . . . . . . . . . .
`23.3 HPLC with supercritical mobile phases .. . .. . .. . . . . .. . . . . .. .. .. .
`
`24 Review papers on the separation of individual classes of
`compounds .. .. . . ... .. . ... .. . .. ... . . . .. .. . . . . .. .. . . . . . . .. .. . . . . . . . .. . .. . ... .. . . . . . . .. .. .
`
`25 Commercially available stationary phases for HPLC ........
`25.1 Porous layer bead adsorbents . . . . . . .. .. .. .. .. . . . .. . . . .. .. .. . .. .. . . . .
`25.2 Silica gels .. .. . .. ... . .. . .. .. . .. . .. . . . . . . . . .. .. . . . . . . . . .. .. . . . .. . . ... . . .. . . . .. . .. .
`25.3 Aluminas ·.........................................................................
`25.4 Other adsorbents . . .... .. .. . . .. .. . .. .......... .. . .. .. .. .. . .. .. . .. .. .. .. . .. ...
`25.5 Non-polar phases chemically bonded to silica (reversed
`phases) ...........................................................................
`25.6 Medium-polar phases chemically bonded to silica .......
`25.7 Porous layer bead ion exchangers (PLBs) ...................
`25.8 Anion exchangers on silica . .. .. . ... . . . .. . . . .. .. . . ..... . .... . . . .. .. . . . .
`25.9 Cation exchangers on silica ...........................................
`25.10 Anion exchangers on styrene-divinylbenzene .. .. .. ... .. ...
`25.11 Cation exchangers on styrene-divinylbenzene .. .. . .... ... .
`25.12 Ion chromatography phases . . . .. .. .. ... .. .... ... .. .. . .... ... . .. .. .. ..
`25.13 Stationary phases for size-exclusion chromatography ..
`25.14 Affinity chromatography phases ...................... ........ ..... ..
`25.15 Special phases for biopolymer separations ... . .. .. ... . . .. . ..
`25.16 Special phases for sugar separations ...........................
`25.17 Phases for special compounds .......................... ............
`25.18 Chiral phases . . .. .. . . . . .. .. . . . .. . . . . . . . . . .. .. . .. . . . . . .. . . . . . . . . . . . . . . .. .. . .. ..
`25.19 List of manufacturers .. .. . .. . .. .. .. . .. .. ... .. . . . .. .. . . . .. .. . .. . . . .. .. . . . . .
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`Exhibit 1011-8
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`xii
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`Index of separations
`
`.............................................. ............................. 303
`
`Index ........................................................................................................ 305
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`Exhibit 1011-9
`IPR2016-00379
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`-
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`25 Commercially Available Stationary
`Phases for hplc
`
`The tables below have been compiled to the best of the author's ability but
`are not guaranteed , as
`it
`is almost
`impossible
`to cover
`the whole
`range available without missing a few out. Some companies a re very
`uncommunicative concerning detailed information. Current catalogues should
`always be consulted as a matte r of course, as available materials are always
`changing. To understand the tables it is necessary to have read Chapter 6.
`Table titles correspond to the relevant section headings. Manufacturers'
`addresses are given in Table 25.19.
`Apart from a few exceptions, only stationary phases with a particle
`diameter of 10 µm and below (plus porous layer beads) have bee n covered . 1
`In some cases the distribution in the various tables is difficult. Some phases
`are only available as packed columns but this has not been noted . The
`designatio n 'manufacture r' is often misleading as some companies are actually
`suppliers and trade other producers' goods under their own name. Lack of
`openness must be complained of in this context.
`Units are not given in the tables, hence for refere nce:
`particle diamete rs are in µm ;
`specific surface areas are in m ~ g- 1;
`pore diamete rs are in nm ;
`irr. = irregular particle shape;
`sph. = spherical particle shape.
`
`25.1 POROUS LA YER BEAD (PLB) ADSORBENTS
`
`Non-polar and medium-polarity PLBs can be found in Tables 25.5 and 25.6
`and ion exchange r PLBs are in Table 25.7.
`
`'For a review on stationary phases with particle diameter > 20 µm see: K. K. Unger and R.
`Janzen , J. Chromatogr., 373, 227 (1986).
`
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`Exhibit 1011-10
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`270
`
`TABLE 25.1
`
`Name
`
`Type
`
`Surface
`area
`
`Particle
`diameter
`
`Manufacturer
`
`Chromosorb LC-2
`Chromosorb LC-3
`Corasil
`HC-Pellosil
`Perisorb A
`Perisorb PA-6
`Yydac Silica
`Zipax
`
`Silica gel
`Alumina
`Silica gel
`Silica gel
`Silica gel
`Polyamide 6
`Silica gel
`Silica gel
`
`15-30
`25-30
`
`14
`
`8
`
`37-44
`37-44
`37-53
`40
`30-40
`30-40
`30
`30
`
`Johns-Manville
`Johns-Manville
`Waters
`Whatman
`Merck
`Merck
`Separations Group
`Du Pont
`
`25.2 SILICA GELS
`
`Only a few manufacturers actually produce si lica gels, hence many of the
`products listed in the table under a company"s name are presumably identical. -
`PLB silica gels can be found in Table 25. 1.
`
`TABLE 25.2
`
`Name
`
`Surface
`area
`
`Pore
`diameter
`
`Particle
`diameter Type Manufacturer
`
`Adsorbosphere Silica
`Baker Silicagel
`Bakerbond Silica Gel
`Bio-Sil HP
`Chromosorb LC-6
`ChromSpher
`CP-MicroSpher Si
`Daltosil 100
`Econosphere Silica
`Hypersil
`Hypersil-WP 300
`ICN Silica
`LiChrosorb Si 60
`LiChrosorb Si 100
`LiChrospher Si 60
`LiChrospher Si 100
`LiChrospher Si 300
`LiChrospher Si 500
`LiChrospher Si I 000
`LiChrospher Si 4000
`Matrex Si 60A
`
`200
`550
`170
`340
`400
`160
`
`300
`250
`170
`60
`500-600
`500
`300
`700
`250
`250
`60
`30
`10
`540
`
`8
`6
`12
`6
`12
`12
`
`12
`JO
`12
`30
`6
`6
`10
`6
`10
`30
`50
`100
`400
`6
`
`3,5, 10
`10
`3,5
`10
`5,10
`5
`3
`4
`5
`3,5,10
`5,10
`3-6.7-12
`5,7, 10
`5,7,10
`4,5, 10
`5, 10
`JO
`10
`10
`10
`5,10
`
`sph.
`trr.
`sph.
`irr.
`irr.
`sph.
`sph.
`sph.
`~ph.
`sph.
`sph.
`irr.
`irr.
`irr.
`sph.
`sph.
`sph.
`sph.
`sph.
`sph.
`sph.
`
`All tech
`Baker
`Baker
`Bio-Rad
`Johns-Manville
`Chrompak
`Chrompack
`Serva
`Alltech
`Shandon
`Shandon
`ICN
`Merck
`Merck
`Merck
`Merck
`Merck
`Merck
`Merck
`Merck
`Am icon
`
`LOWER DRUG PRICES FOR CONSUMERS, LLC
`Exhibit 1011-11
`IPR2016-00379
`
`

`
`TABLE 25.2 cont.
`
`271
`
`Name
`
`Surface
`area
`
`Pore
`diameter
`
`Particle
`diameter Type Manufacturer
`
`320
`320
`550
`
`>400
`500
`350
`200
`100
`35
`25
`10
`350
`160
`500
`300
`100
`35
`300-350
`200
`300
`400
`550
`450
`
`Matrex Si lOOA
`Matrex Si 250A
`MicroPak Si2
`MicroPak Si-150
`MicroSil
`Nucleosil 50
`Nucleosil 100
`Nucleosil 120
`Nucleosil 300
`Nucleosil 500
`Nucleosil 1000
`Nucleosil 4000
`Partisil
`PartiSphere Silica
`Polygosil 60
`Polygosil 100
`Polygosil 300
`Polygosil 500
`µPorasil
`Resolve Silica
`Resolvex SIL
`RoSil Silica
`RSil Silica
`Separon SGX
`Sepralyte SI
`Serva Si 60
`Serva Si 100
`Serva Si 300
`Serva Si 500
`Shodex Silicapak
`Spherisorb SW
`Spherosil XOA 600
`Spherosil XOA 800
`Supelcosil LC-Si
`Supelcosil LC-3-Si
`Superspher Si 60
`Techsil Silica
`TSK Typ LS SIL
`Ultrasil-Si
`Ultrasphere-Si
`Versapack Silica
`Vydac HS 101 Silica 500
`Vydac TP 101 Silica 90
`YMC Silica
`Zorbax SIL
`
`220
`540-660
`720-880
`170
`100
`670
`385
`
`180
`
`350
`
`2. Identical with LiChrosorb SI 60.
`
`10
`25
`6
`15
`<6.5
`5
`10
`12
`30
`50
`100
`400
`8.5
`12
`6
`10
`30
`50
`12
`9
`8
`8
`6
`10
`
`6
`10
`30
`50
`
`8
`6
`4
`IO
`30
`6
`8
`
`8
`
`8
`30
`10
`7-8
`
`5,10
`5,10
`5,10
`5
`<7
`5,7,10
`3,5,7,10
`3,5,7,10
`5,7 ,10
`5,7,10
`5,7,10
`5,7,10
`5,10
`5
`5,7,10
`5,7,10
`7
`7
`10
`5.10
`10
`3,5,8
`5,10
`7,10
`5, 10
`3,5,10
`3,5,10
`3,5,10
`10
`5
`3,5,10
`5-7
`5- 7
`3,5
`5
`4
`5,10
`5,10
`10
`5
`10
`5,10
`5,10
`3,5
`3,5,7
`
`sph. Am icon
`sph. Am icon
`irr.
`Varian
`sph. Varian
`sph . Micromeritics
`sph. Macherey-Nagel
`sph. Macherey-Nagel
`sph. Macherey-N a gel
`sph. Macherey-Nagel
`sph. Macherey-N a gel
`sph. Macherey-Nagel
`sph. Macherey-Nagel
`irr. Whatman
`sph. Whatman
`irr. Macherey-Nagel
`irr. Macherey-Nagel
`irr. Macherey-Nagel
`irr.
`Macherey-Nagel
`trr. Waters
`sph. Waters
`sph.
`Fisher Scientific
`sph. Alltech
`irr.
`All tech
`sph.
`Reichelt
`sph. Analytichem
`irr.
`Serva
`irr.
`Serva
`irr.
`Serva
`1rr.
`Serva
`sph.
`Showa Denko
`sph.
`Phase Separations
`sph.
`Prolabo
`sph.
`Prolabo
`sph .
`Supelco
`sph.
`Supelco
`sph. Merck
`1rr.
`hplc
`sph.
`Toyo Soda
`irr.
`Beckman
`sph. Beckman
`1rr.
`All tech
`sph.
`Separations Group
`sph.
`Separations Group
`sph. YMC
`sph. Du Pont
`
`LOWER DRUG PRICES FOR CONSUMERS, LLC
`Exhibit 1011-12
`IPR2016-00379
`
`

`
`272
`
`25.3 ALUMINAS
`PLB aluminas can be found in Table 25.1.
`
`TABLE 25.3
`
`Name
`
`Surface Pore
`diameter
`area
`
`Particle
`diameter
`
`Type Surface
`reaction Manufacturer
`
`155
`Alox 60
`60
`Aluminiumoxid 60
`200
`ICN Alumina
`LiC hrosorb Alox T 70
`93
`Spherisorb A Y
`60
`Techsil Alumina
`
`6
`6
`6
`15
`13
`6
`
`5, 10
`5,10
`3-6,7-12
`5,10
`5, 10
`5, 10
`
`irr.
`irr.
`irr.
`irr.
`sph.
`irr.
`
`basic
`basic
`neutral
`basic
`
`acidic
`
`Macherey-Nagel
`Reichelt
`JCN
`Merck
`Phase Separations
`hplc
`
`25.4 OTHER ADSORBENTS
`
`TABLE 25.4
`
`Particle
`diameter Comments
`
`Manufact urer
`
`Name
`
`ACT-I
`
`ACT-2
`
`Type
`
`Polymer with
`octadecyl phase
`Vinylpyridine polymer
`
`Bio-Gel HPHT
`
`Hydroxylapatite
`
`Buffered Silicagel
`
`Citrate-buffered silica
`
`CEL AC-40 XF
`Chromex DN-X2
`Chromex DN-X8
`Chromex DN-X12
`Chromex HEMA
`HN-X20
`Dynosphcre PD
`Gynkochrom
`
`Hamilton PRP- 1
`
`Triacetylcellulose
`Styrene-2% divinylbenzene
`Styrene-8% divinylbenzene
`Styrene-12% divinylbenzene
`Polyhydroxyethyl
`methacrylate
`Styrene-divinylbenzene
`reversed phase
`on alumina
`Styrcne-<livinylbenzenc
`
`PA-6
`Pentax PEC 101
`
`Polyamide-6
`Hydroxylapatite
`
`10
`
`II
`
`10
`
`5
`
`7
`I I
`II
`11
`11
`
`hydrophilic
`
`Interaction
`
`Interaction
`
`Bio-Rad
`
`Waters
`
`pH 0-14,
`max. 200 bar
`pH 0- 14,
`ionizable
`for proteins,
`nucleic acids
`max. 14 bar
`for polar acidic
`compounds, see
`Fig. 9. 10
`40% acetyl content Macherey-Nagel
`Dionex
`Dionex
`Dionex
`Dionex
`
`5.10
`5
`
`5,10
`
`5-20
`2, 10
`
`to pH > 12
`
`415m 2 g I
`for reversed and
`normal phase
`irr.
`for proteins.
`
`Dyno
`Gynkotek
`
`Hamilton
`
`Macherey-Nagel
`Asahi
`
`LOWER DRUG PRICES FOR CONSUMERS, LLC
`Exhibit 1011-13
`IPR2016-00379
`
`

`
`TABLE 25.4 cont.
`
`273
`
`Name
`
`Type
`
`Particle
`diameter Comments
`
`Manufacturer
`
`PLRP-S
`
`Styrcne-<livinylbenzene
`
`RoGel
`RoGel-PI
`
`St} renc-<livinylbenzene
`Styrene-divinylbenzene
`with polyalcohol
`Shodcx RSpak DC Styrcnc-divinylbcnzcne
`with ionic phase
`Shodex RSpak DE Polymcthacrylate
`Shodex RSpak DM Polyhydroxy methacrylate
`Shodex RSpak DS
`Styrenc-<livinylbenzenc
`Triacetylcellulose
`Tnacetylcellulose
`We!.ean RP R
`Styrcne--divinylbenzene
`
`5.8.10
`
`nucleic acid'>.
`max. 150 bar
`pore diameter
`10.30.100 nm
`3,5.8, 10 8 nm pore
`3,5.8,10 water compatible
`
`Polymer
`Laboratories
`Alltech
`Alltcch
`
`hydrophilic
`
`Showa Denko
`
`medium polar
`hydrophilic
`hydrophobic
`
`for anionic sur-
`factants and anion'>
`strongly bonded on
`ion exchangers
`
`Showa Denko
`Showa Denko
`Showa Denko
`Merck
`Wescan
`
`10
`IO
`
`25.5 NON-POLAR PHASES CHEMICALLY BONDED TO
`SILICA (REVERSED PHASES)
`
`In most cases, the silica starting materia l of a specific phase can be
`determined from Table 25.2. Should this not be clear, then the starting
`material is listed, if known. Further non-polar silica phases can be found in
`Tables 25.15, 25. 16 and 25.17.
`
`TABLE 25.5
`
`Name
`
`Functional
`group
`
`Type
`
`Particle
`diameter
`
`Comment>
`
`Manufacturer
`
`Adsorbosphcre C 1•
`Adsorbosphere c.
`AdM>rbosphere Phenyl
`Aquapore BU-300
`Aquapore PH-300
`/\quapore RP-300
`Baker Octadecyl
`Baker Octyl
`Baker Butyl
`Baker Cyclohexyl
`Baker Phenyl
`Bakerbond Octadecyl
`
`sph.
`Octadecyl
`sph.
`Octyl
`sph.
`Phenyl
`sph.
`Butyl
`sph.
`Phenyl
`sph.
`Octyl
`irr.
`Octadecyl
`irr.
`Octyl
`irr.
`But vi
`Cyciohexyl irr.
`Phenyl
`irr.
`Octadecyl
`sph.
`
`3.5.10
`3,5,10
`5.10
`10
`10
`10
`10
`10
`10
`10
`10
`3.5
`
`All tech
`All tech
`All tech
`Brownlee
`30 nm pores
`Brownlee
`30 nm pores
`30 nm pow,
`Brownlee
`Baker
`end-capped. I 8'YoC
`Baker
`end-capped. 6%C
`end-capped, 4.2°uC Baker
`end-capped. 5%C
`Baker
`end-capped. 7%C
`Baker
`Baker
`end-capped. 13% C
`
`- Cont.
`
`LOWER DRUG PRICES FOR CONSUMERS, LLC
`Exhibit 1011-14
`IPR2016-00379
`
`

`
`274
`
`TABLE 25.5 cont.
`
`Name
`
`Functional
`group
`
`Type
`
`Particle
`diameter
`
`Comments
`
`Manufacturer
`
`Bakerbond Octyl
`Bakerbond Phenylethyl
`Bio-Sil ODS-10
`Bio-Sil ODS-SS
`µBondapack c,.
`µBondapak Phe nyl
`Bondapak C, 8/Corasil
`Bondapa k Phcnyl/Corasil
`Chromosorb LC-4
`Chromosorb LC-5
`Chromosorb LC-7
`Chromosorb LC- 10
`ChromSpher Cl8
`ChromSpher C8
`CP-MicroSphcr C l8
`Diphenyl =Si
`Econospherc Cl8
`Econosphcre C8
`Gynkochrom MH- I
`HD-SIL-18-Ss
`HD-SIL-18- 10
`ODS-Hypersil
`MOS-Hypersil
`SAS-Hypersil
`
`Phenyl-Hypersil
`Hypersil WP300 Octyl
`Hypersil WP300 Butyl
`ICN Silica RPl 8
`ICN Silica RPl 8
`ICN Silica RPS
`LiChrosorb RP-18
`LiChrosorb RP-8
`LiChrosorb RP-2
`LiChrospher 100 RP- 18
`LiChrosphe r 100 RP-8
`LiChrospher RP-8
`LiChrospher RP-1 8( e)
`LiChrospher RP-8(e)
`Matrex Cl8
`Matrex C8
`MicroPak MCH
`
`sph.
`Octyl
`sph.
`Phenyl
`irr.
`Octadecyl
`sph.
`Octadecyl
`irr.
`Octadecyl
`irr.
`Phenyl
`.PLB
`Octadecyl
`PLB
`Phenyl
`Octadecyl PLB
`PLB
`Phenyl
`Octadecyl
`irr.
`Octyl
`1rr.
`Octadecyl
`sph .
`Octyl
`sph .
`Octadecyl
`sph.
`Diphe nyl
`irr.
`Octadecyl sph.
`Octyl
`sph.
`Octadecyl sph.
`Octadecyl sph.
`Octadecyl
`irr.
`Octadecyl sph.
`Octyl
`sph.
`Tri methyl
`sph.
`
`sph.
`Phenyl
`sph.
`Octyl
`sph.
`Butyl
`Octadecyl sph.
`Octadecyl
`irr.
`Octyl
`Irr.
`Octadecyl
`irr.
`Octyl
`lff.
`Dimethyl
`irr.
`Octadecyl
`sph.
`Octyl
`sph.
`sph .
`Octyl
`Octadecyl
`sph .
`sph .
`Octyl
`Octadecyl
`sph.
`Octyl
`sph.
`Octadecyl
`irr.
`
`5
`5
`10
`5
`IO
`JO
`37-50
`37-50
`37-44
`37-44
`5,10
`
`5
`5
`3
`3,5,10
`5
`5
`5
`5
`IO
`5
`5
`3,5,10
`
`3,5,10
`5,10
`5,10
`6-8
`7-12
`7-12
`5,7, 10
`5,7,10
`5,7,10
`5,10
`5,10
`10
`5,10
`5, 10
`5,10
`5,10
`5,10
`
`MicroPak MCH-N-Cap
`MicroPak SP C-18
`
`Octadecyl
`Octadecyl
`
`irr.
`sph .
`
`5
`3,5
`
`MicroPak SP-C8 IP
`Micro Pak ODS-120A
`
`Octyl
`Octadecyl
`
`sph.
`sph .
`
`MicroPak ODS- 120T
`
`Octadecyl
`
`sph.
`
`MicroPak ODS-80TM
`
`Octadecyl sph.
`
`5
`5
`
`5
`
`5
`
`MicroPak TMS-250
`
`Tri methyl
`
`sph.
`
`10
`
`end-capped, 7%C
`e nd-capped, 4.5%C
`end-capped
`non-capped
`from µPorasil
`end-capped
`
`15%C
`
`10 and 30 nm pores
`end-capped
`e nd-capped
`polymer, 18%C
`
`for polar and multi-
`functional samples
`
`Baker
`Baker
`Bio-Rad
`Bio-Rad
`Waters
`Waters
`Waters
`Waters
`Johns-Manville
`Johns-Manville
`Johns-Manville
`Johns-Manville
`Chrompack
`Chrompack
`Chrompack
`Seiva
`All tech
`All tech
`Gynkotek
`Organogen
`Organogen
`Shan don
`Shandon
`Shandon
`
`Varian
`Varian
`
`Shandon
`Shandon
`pore diameter 30 nm
`pore diameter 30 nm
`Shandon
`ICN
`pore diameter 30 nm
`ICN
`pore diameter 6, 10,25 nm
`pore diameter 6, 10 nm
`ICN
`Merck
`from LiChrosorb SI 100
`from LiChrosorb SI JOO
`Merck
`Merck
`from LiChrosorb SI 60
`10 nm pores
`Merck
`Merck
`10 nm pores
`pore diameter 50, 100,400 nm Merck
`end-capped
`Merck
`end-capped
`Merck
`Amicon
`} pore diameter
`Ami con
`6.10,25 nm
`pore diameter 6 nm ,
`Varian
`non-capped
`end-capped
`pore diameter 10 nm.
`end-capped
`end-capped
`pore diameter 12 nm .
`non-capped
`pore diameter I2 nm ,
`e nd-capped
`pore diame te r 8 nm,
`e nd-capped
`pore diameter 25 nm,
`e nd-c