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judge0zz8 发表于 2008-1-10 14:04

液质联用分析药物

CONTENTS
^(ez}7KB Preface ix
`sjp2e3_5? Acknowledgments xiNG `.C Eii~
1. Introduction 1
w#m4pR p9N/Od%L Emerging Analytical Needs / 1
w,@:K:X jU Integration of LC/MS into Drug Development / 3oF m$A[,['I
Partnerships and Acceptance / 6
D_#A!EQV!Qv*d Overview / 10N.ro pw9fo
2. Drug Development Overview 11'a7rXP:brXCqm8D)a~'^
Analysis Perspectives / 11@S/S:C-o1A5^s x
The Four Stages of Drug Development / 12"cXm[#]4bT%dmD3{
Drug Discovery / 14
"O }&z1h+N_D Preclinical Development / 15 C&ul)H@_7c
Clinical Development / 16~$Zw'H p5i
Manufacturing / 17
Ih9c J ^Az m 3. Accelerated Drug Development 19
gCM'|\ Accelerated Development Strategies / 20
p;K^^i4U| u Quantitative and Qualitative Process Elements / 20
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vi CONTENTS%vT't*E MG"U*u9]`
Quantitative Process Pipeline / 24%C)Y l9X |+B#V i9@.d
Qualitative Process Pipeline / 25a$z6Q2d8nT$r _*f
Motivating Factors / 27
fR4}F!Z+QB/v#r Analysis Opportunities for Accelerated Development / 28 W#Y&V.{+`7rs$R
Full-Time Equivalent / 28
B9v9k:V?k5H0cM Sample Throughput Model / 29
[
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yw4rO&Z2qL Elimination Model / 29k+|q+\ m
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Rate-Determining Event Model / 31
%Tu UE E`~ g(|d ]E Accelerated Development Perspectives / 33
y8n(Ec I-E~ 4. LC/MS Development 34
L4`g^+nI The Elements of LC/MS Application / 34
NVo%n"g/bNP HPLC / 35
2O4m*P6NM Mass Spectrometry / 35kv]R _ t
LC/MS Interface / 36
;NBXhbm.w LC/MS Growth / 38G2bQ?Bm@9@8X
5. Strategies 41
C,Z.U uh"~,y([ Standard Methods / 43%cAM~luFewEx
Template Structure Identification / 46
*c)url0U'l0{ Databases / 49a4B1fI1_ m$I
Screening / 50)G:]j%Z@R k;d
Integration / 53
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}`k0[7n Miniaturization / 55
6|_K({~A Parallel Processing / 56
y%G I)TN sq6f+['l Visualization / 58/Q$y sG.oc?
Automation / 61
;Tl,t-t8U8Cg2vbX Summary / 63B4kVwTL#Z C#tp
6. LC/MS Applications 65\F"z;v'h/J${i*f.gf
Drug Discovery / 65
B1V"d.K!s:p)c4b Proteomics / 68
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xvR Protein Expression Profiling / 70
vir*Ab'c~$lZ Quantitation / 76
+h CFR"X&a+H%[ CONTENTS vii@U
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Glycoprotein Mapping / 78
/N^%mD'?2W$Z Natural Products Dereplication / 83fR!?(GeM cs8d:B
Lead Identification Screening / 88nzQD7V|
Bioaffinity Screening / 892Q4a'F+TE\W.D4w?'lN;Z
Combinatorial Library Screening / 92;UVtGn {}1y
Open-Access LC/MS / 96
6K| n,K\x8E Structure Confirmation / 97Ad5}Ht
High Throughput / 100:I&Vi)J4Tc"h i
Purification / 102MkS}ZS8hP"~uYk
Combinatorial Mixture Screening / 103
4E jT@ c8w In Vivo Drug Screening / 106p*An*vI)~
Pharmacokinetics / 109
)rnNg6tE In Vitro Drug Screening / 115
RHnQZ Metabolic Stability Screening / 118
)\'UJn(UIdh ?(_~ Membrane Permeability / 1191\0B-mw}B7r:Zd
Drug-Drug Interaction / 1213Mx7xS(s_sL
Metabolite Identification / 122|k8]
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Preclinical Development / 123

~)A~3{.msV4{l Metabolite Identification / 125k4Q
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Impurity Identification / 1321V;mn)o}GL;~1t
Degradant Identification / 140
.g&euEW7M m Clinical Development / 145Nl{@*wGy@$C\
Quantitative Bioanalysis—Selected Ion Monitoring / 148
1Kc+hMh1K
g7~ Quantitative Bioanalysis—Selected Reaction 2}r!M{B~9s
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Monitoring / 152
:C whH,j6bLf2i:X Quantitative Bioanalysis—Automated Solid-Phase
g6c3Zs9sp5| Extraction / 156
zdZ'w2kC~({,Jq5[ Quantitative Bioanalysis—Automated On-Line ;E;]oQKNxs(o'FN
Extraction / 162
:t:nb.LUgd Metabolite Identification / 165"f1yFdDAQ
Degradant Identification / 168,_1pO?
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Manufacturing / 171&A&P^!b.W H{/Q9m
Impurity Identification Using Data-Dependent
*z,V;jAw Analysis / 173
4RN^/O;ZR;a3n&| @ viii CONTENTS6h.VC4s1c;Iu
Peptide Mapping in Quality Control / 176(VwS/W4e@
Patent Protection / 178i,@"Fl)e
7. Future Applications and Prospects 183$Tp5d1m`1}{V
Workstations / 183
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c*J:O!xE%f$q'z Multidimensional Analysis / 186{pnE? |#W9BT
Miniaturization / 187
*BC;l9?shk Information Management / 189
`Z+~:`\L;?8ZH\:V Strategic Outsourcing / 190
)|3SDJI~gNS Summary / 191
(Gv0f-n*oa0\ v 8. Perspectives on the Future Growth of LC/MS 192
zD`5M3?+ip1K3sK1p 9. Conclusions 195
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_,sB*N8aK Glossary 197
A;A1\E)?,V-z2bWjm References 2057]{ jdXSU,y5o
Index 235
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