,,, (M S) ; 1934 ; M o rell. ; 1918, D em p ster Tsinghua Tongfang Optical Disc Co., Ltd. All rights reserved.

Transcript

1 Journal of Ch inese M ass Spectrom etry Society V o l. 23 N o. 4 N ov (, ) [ ]:,, 1975, 1998, : g (M atrix2assistant laser deso rp tion ionization tim e2of2 fligh t m ass spectrom etry, M ALD IgTO FM S) (E lectrode sp ray ionization m ass spectrom e2 try, ES I2M S), : ; ; ; ; ; : O ; R 917 : A : (2002) [ 1 (M S) ], ; 1934, 2 (GCgM S), (H PL CgM S) g (SFCgM S), (M SgM S), ;,,,,, 235 U, ; , T hom son [ 1 ] 1957 M o rell, Ho lm es 2 ; 1918 D em p ster 180, 2, : : (1975 ), ( ),, E-ma il: llxxddoo75@ sohu. com

2 4 235 [ 6, (SD S2PA GE) ] [ 2 4 ] 30,, 1981 Bar2,, ber (FBA 2M S),,,, 1984, John Fnnn, (ES I2M S), 4 M X2, 1988 T anaka H il2 [ 7, 8 lenkam p N 2(42 ) ] g (M ALD IgTO FM S) M ALD I 112,,,,,, GCgM S H PL CgM S, (FT gicr 2M S) 2 ( ), [ 9 ], SFC2M S M SgM S [ 10 ] M S FAB (HR FAB ) E I (HR E I), ( IR ), 2 2 (UV ) (NM R ) X2 (L CgNM R gm S), GCg M S,, : 3 4 h, 86% [ 11 ] M S UV IR 2 NM R, 113 [ 5 ] 1, 111, H PL Cg GCgM S M S,,, H PL C L CgM S, 2 (L CgES I2M S), 2 L CgM S

3 , L CgM S L 2 g L 2 g ES I2M S , 2 2, , %, SD S2PA GE,,,, SD S2 PA GE,,, M ALD IgTO FM S 2 L - g ESI-M S [ 12 ] F ig. 2 ESI-M S and m olecular we ight of L -asparag inaseg, L CgM S, L CgM S GCg M S, L CgM S,, T S2L CgM S, [ 14, 15, ] 1, LCgM S, L CgM S F ig. 1 TIC of the LCgM S-ac id degradation product of clar ithrom yc in,,,, L CgM S 114, ES I,, M ALD I, ES I A PC I [ 13 ] [ 16 ], Poon GK [ 17 ] [ 14 ] ES I L CgM S 21, 8 (L im onene) 5 ; Tom lin son [ 18 ] ES I CEgM S ; H aloperido 2 M SgM S L CgM SgM S

4 4 237,,, F. Streit [ 19 ] ES I2M SgM S C, (C ID ) ; Poon GK [ 20 ] L CgM SgM S,, 2, 2,, 2 M ALD I2M S, ES I2M S [ 22 ], [ 23, ] [ 24 2 ] (PTM ), [ 25 Jon scher ] M ALD I2 (M ALD IgQ IT 2M S) P M ath2 ias W ind [ 26 ], ES I M ALD I, ICPgM S 31 P,, ES IgQ IT 2M S [ 27 ], M ALD IgTO FM S,,, [ 21 ] H PL CgES I2M S 211,,,, CEgES I2M S Q 2, Star (ES I2Q qto F) M ALD I2M S,,,, (2D 2, 5 ΛD [ 28 ], PA GE) (L ys) (Gln), [ 29 ], N, M SgM S H PL CgM S ( M SgM S),

5 , H PL C L CgM S, [ 30 ], M ALD IgTO FM S [ 31 ],,, L Cg UV gm S L 2 g 3 M ALD I2M S, Edm an M ALD I2M S 3 L - g F ig. 3 Peptide diagram of L -asparag inaseg by N C trypsin degrada tion [ 32 N C ] 213 : (1), ; M ALD I2M S ES IgM S ( 2) [ 33, 34 ], ; (3), ; (4) [ 36 M ALD Ig, ] TO FM S, 12 60, M ALD I2M S 0. 1%, 10 4 ES I2M S, [ 37 ] M ALD IgTO FM S 3 (DNA ) (RNA ) [ 35 ] :,

6 [ 9 ] Silw ar R. A naltical T echniques fo r the Investiga2 tion of Coffee A rom a [J ]. T rends in A nalytical Chem istry. 1982, 1 (13): [ 10 ],,,.,, [J ]., 2001, 22 (3): 15, 20. [ 11 ],,,. [J ]., 2000, 11 M ALD I2M S ES I2M S (2): , [12 ]. [M ]. :,, 2001: , [ 13 ]. [M ]., :, 1990: [14 ]. 21 [M ]. :, 2001: , [15 ] John JL angnfend, Stenve B, H aw tho rne, et al.., D ifferen tial Exp ression of Basal and H ydrocar2 bon2induced Cytoch rom e P2450 M onooxygenase and R eductase A ctivities in Subpopu lation s of M urine Ep iderm al Cells D iffering in T heir Stages of D ifferentiation [J ]. D rug M etab D ispo s, 1992 (20): , [ 16 ] Rozm an E, Douglus K Sp ruck lin, K Enneth E [ 38, 39 ], T humm el, et al. H um an R eductive H alo thane M etabo lism in V itro is Catalyzed by Cytoch rom e P450 2A and 3A 4 [J ]. D rug M etab and D isp, 1996, 23 (9): [17 ] Poon GK, V igush in D, Griggs L J. et al. Identi2 : fication and Characterization of L im onene [ 1 ],. ( ) M etabo lites W ith A dvanced Cancer by L iqu id [M ]. : : 2000: 1 8. [2 ] Do rsey JA, H unt RH, O neal M J. R ap id2scnning Ch rom atographygm ass Spectrom etry [ J ]. M etab and D isp, 1996, 24 (5): D rug M ass Spectrom etry Continuous A nalysis of F rac2 [ 18 ] Tom linson A J, L inda M B, Kenneth L J. Investi2 tions F rom Cap illary Gas Ch rom atography [ J ]. A nal Chem, 1963 (35): gation of the M etabo lic Fate of the N euro tep tic D rug H aloperido l by Cap illary E lectropho resie2 [ 3 ] W aston JT, B iem ann KB. H igh2r eso lution M ass E lectro spary Ionization M ass Spectrom etry[j ]. J Spectra of Com pounds Em erging F rom a Gas Ch rom atogr (B iom ed A pp l), 1993, (621): 239 Ch rom atograph[j ]. A nal Chem, 1964 (36): [ 19 ] Streit F, U Ch ristians, B D isdier, et al. Struc2 [ 4 ]. [M ]. :, 1983, [ 5 ],. ( ) tural Identification of T h ree M etabo lites and a D egradation P roduct of the M acro lide Imm uno2 supp ress ant Siro lim us (R apam ycin) by E lectro2 [M ]. : : 2000: 7 8. [6 ] K im SH,L ee JH, Yun SY, et al. R eaction M oni2 sp ray2m SgM S A fter L iver M icro som es [J ]. Incubation W ith H um an D rug M etab and D isp, to ring of Succinylation of Co llagen W ith M atrix2 1996, 24 (11): A ssisted L aser D eso rp tiongionization M ass Spec2 [ 20 ] Poon GK, YC Chui, R M ccague, et al. A nalysis trom etry [ J ]. R ap id2comm un2m ass2spectrom. of Phase g and Phase g M etabo lites of T amox2 2000, 14 (22): ifen in B reast Cancer Patients [J ]. D rug M etab [ 7 ],. M Z22 and D isp, 1993, 21 (6): N 2(42 ) [J ]. [ 21 ]. g (ES I2M S), 1989, 20 (6): [ 8 ]. [M ]., 2001: : [J ]., 2002, 19 (2): [22 ]. [M ]. :

7 240 23, 2002: [23 ]. 21 [M ]., 2001: [ 24 ] M clafferty FW, Ziqing Guan, U lrich H aup tṡ : Gasou s Confo rm ational Structu res of Cy2 toch rom e c[j ]. Am Chem Soc, 1998, 120: [25 ] Jonscher KR, Yates JR. M atrix2a ssisted L aser D eso rp tiongion ization M ass Spectrom etry of Pep tideṡ B io l Chem, 1997, 272: [26 ] M ath iasa W ind,m ichael Edler,N o rbert Jakubo2 w sk i, et al. A nalysis of P ro tein Pho spho rylation by Cap illary L iquid Ch rom atography Coup led to E lem ent M ass Spectrom etry W ith 31 P D etection and to E lectro sp ray M ass Spectrom etry [ J ]. A nalytical Chem istry, 2001, 70 (1): [27 ],,. 2 TO F M ass Spectrom etry D etection [ J ]. Chem, 2002, (74): A nal [J ]. [ 36 ],. : C, 2000, 30 (4): [ 28 ] Ch irstine Enjalbal, Jean M artinz, Jean2L ouis A ubagnac. M ass Spectrom etry in Com binabo ri2 al Chem istry[j ]. M ass Spectrom etry R eview s, 2002, 19 (3): [29 ],,,, ES I2Q TO F M S) [J ]. A nal B ioanal Chem, 2002, (372): [A ]. [ 38 ],,. GC2M SD (S IM ) [C ]., M L T [J ].. [ 30 ],,,. 2002, 23 (1): H PL CgES I2M S [J ]. [39 ],,. GCg. 2000, 31 (6): [ 31 ],,,. H PL C M AL 2 D I2TO F2M S [J ] , (21) 3 4 : [ 32 ]. [M ]. :, 2002: [ 33 ] M ech ref Y, N ovo tny M V, M ass Spectrom etry and Sequning of N 2L inked O ligo saccharides D e2 rived F rom Subm icrogram Am oun t of Glyco2 p ro teins [ J ]. A nal Chem, 1996, 68: [ 34 ]. [M ]. :, 2002: [ 35 ] Berggren W T, T setska T akova, M arilyn CO l2 son, et al. M ultip lexed Gene Exp ression N lysis U sing the Invader RNA A ssay W ith M ALD I2 [A ]. [C ]., [ 37 ] Jo seph J D alluge. M atrix2a ssisted L aser D es2 o rp tiongionization M ass Spectrom etry (M ALD I2 M S [J ] , 22 (3): The Rev iew of M a ss Spectrom etry Applied in New D rug Investiga tion L IAN G X iao2dong (Institu te of R ad iation M ed icine, A cad em y of M ilitary M ed icine S ciences, B eij ing , Ch ina) Abstract: Som e app lication s of m ass spectrom etry in new develop ing drugs investigation, including syn thesis p rocedu re, co rrobo ration of chem ical structu re, quality con tro l and drug m etabo lism are review ed. T he research p rogress of variou s in strum en ts such as typ ical m atrix2assistan t laser des2 o rp tion ion ization tim e2of2fligh t m ass spectrom etry (M ALD IgTO FM S), electrode sp ray ion ization m ass spectrom etry (ES I2M S) and their techno logies u sed together in b iom acrom o lecu le drugs, iden2 tification of p ro tein, po lypep tide, am ino acid, DNA, RNA are summ arized. M eanw h ile, the b road p ro spects in m ass spectrom etry in living science are view ed. key words: m ass spectrom etry; new drugs investigation; review ; drug syn thesis; structu re co rrob2 o ration; drug m etabo lism