Technical Report. Profiling Trace Volatile Compounds in Blood by Gas Chromatograph Mass Spectrometry with Dynamic Headspace Extraction.

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1 C146-E291 Technicl Report Profiling Trce Voltile Compouns in Bloo y Gs Chromtogrph Mss Spectrometry with Dynmic Hespce Extrction Shoji Kkut 1, Eiichiro Fukuski 1, Tkeshi Bm 1, 2 Astrct: Vrious types of voltile sustnces re present in loo, n in ition to those tht ply roles in the formtion of ucts such s proteins n nucleic cis, some re known to ct s seconry messengers tht regulte vrious iologicl functions. To lern more out these roles, the profiling of voltile components in loo hs een ttrcting ttention. Up to now, soli phse micro-extrction (SPME) n HS-SPME hve een the primry methos use for nlysis of voltile sustnces. The HS-SPME metho is sttic metho in which fier cote with soli (sorent) extrction phse is expose to the gs phse. Becuse extrction procees se on the equilirium migrtion of voltile components, those voltile components tht exhiit strong interction with the extrction fier present strong profile. In this report, we focuse on the ynmic hespce (DHS) metho. The DHS metho is ynmic extrction metho in which the gs phse is forcily purge using n inert gs, n the voltile components re collecte on the sorent. Since nerly ll of the gs phse components cn e collecte, voltile components re efficiently collecte, enling wier rnge of components to e nlyze y this metho compre with conventionl methos. Using stnr mixture of voltile sustnces, comprison of the results of voltile sustnce profiling otine using the HS-SPME n DHS methos showe tht ppliction of the DHS metho permitte etection of ll the voltile sustnces, incluing the lcohols, which were ifficult to profile y HS-SPME. Furthermore, the results of vlition of the DHS metho confirme the etection of ll of the voltile components t ng levels. The results otine pplying this system with IL- knockout mice plsm confirme the etection of 40 voltile compouns, in which significnt ifference etween smples ws oserve with respect to compouns. High-sensitivity voltile sustnce profiling is possile using this system, n is expecte to e pplie in future clinicl reserch. Keywors: GC-MS, Metolomics, Voltile, Dynmic Hespce Extrction 1. Introuction Hespce microextrction, HS-SPME, hs typiclly een pplie in Vrious types of voltile sustnces re present in loo, n some of the istinctive oors originting from loo hve long een mens of istinguishing mong iseses. For exmple, it is known tht increse levels of ketones such s cetone in the loo of ietic ptients prouce n pple-like sweet oor. It is thought tht ientifiction of these kins of isese-specific voltile sustnces might permit the use of such voltile sustnces s iomrker cnites. For exmple, mlonilehye n 4-hyroxy-2-nonenl re ttrcting ttention s oxitive stress mrkers. In ition, the presence of such sustnces s hexnl n nonnl in the loo of lung cncer ptients hs lso een reporte. In recent yers, it hs ecome cler tht the confusion or mutgenesis tht occurs in the intrcellulr signl trnsuction system is ue to the formtion of ucts such s proteins n nucleic cis, n such formtion is cuse y voltile components. These components re now known to e involve in the regultion of iologicl functions s seconry messengers. For exmple, it hs een reporte tht they re involve in mcrophge fom cell formtion tht occurs in the ccelertion of gene expression n the onset of rteriosclerosis. Voltile components iffuse into reth n urine vi the loo, so there is resonle expecttion tht erly ignosis, etermintion, n long-term monitoring of tissue isorers n iseses will ecome possile y nlyzing the voltile components in loo. the mesurement of voltile sustnces (Fig. 1). This metho utilizes piece of fier tht is chemiclly one or cote with polymer or sorent. The liqui smple, which is sele in the vil together with the cote fier suspene ove the liqui, is wrme to trnsfer the voltile components to the vpor phse, therey exposing the vpor phse to the sorent-cote SPME fier, n permitting extrction n concentrtion of the voltile components. Extrction is possile whether the smple is in soli, liqui or gs form, n ecuse of this simple opertion from extrction to nlysis, this technique hs een pplie to vrious types of smples. However, since the HS-SPME metho is sttic extrction metho tht is epenent on the prtition coefficient of the voltile components n the coting phse, when the smple contins mny contminnts, s in the cse of loo, low recovery rtes of voltile components hs een prolem. Prticulrly in the cse of voltile components hving hyroxyl group such s lcohols, reuce etection sensitivity hs een prolem ue to esy istriution in the liqui phse s result of mutul interction with wter. Equilirtion t high temperture mkes it possile to force voltile components into the gs phse, ut since the extrction fier is lso expose to high temperture t this time, overll etection sensitivity is lowere, s hs een reporte. Thus, the profile of voltile components otine using the HS-SPME metho hs wekness in tht voltile components tht exhiit strong interction with the extrction fier present strong profile. 1 Division of Avnce Science n Biotechnology, Grute School of Engineering, Osk University 2 Reserch Center for Trnsomics Meicine, Meicl Institute of Bioregultion, Kyushu University 1

2 There is ynmic extrction metho for voltile sustnces referre to s the ynmic hespce (DHS) metho (Fig.1). The DHS metho is ynmic extrction metho in which voltile gs phse sustnces re forcily purge using n inert gs, n the voltile sustnces re collecte on n sorent. As the HS-SPME metho is se on equilirium migrtion in the liqui phse, gs phse n coting phse, the istriution equilirium fluctutes ue to chnges in temperture or pressure. With the DHS metho, nerly ll of the gs phse portion cn e collecte in the sorent y purging the gs phse, therey permitting efficient collection of the vrious voltile DHS sustnces. Becuse the voltile sustnces contine in the loo vry wiely n re present in extremely smll quntities, the DHS metho, which cn efficiently collect wie vriety of voltile sustnces, is consiere to e very suitle s pretretment metho for comprehensive nlysis of voltile sustnces in loo. In this report, we compre the SPME n DHS methos using stnr smple of voltile components, n then conucte vlition of the DHS metho using stnr mixture of voltile components. Finlly, we conucte nlysis of the voltile components present in mouse serum using DHS-GC-MS. HS-SPME Split Column Asorent Smple extrction Desorption t GC injection port Item Feture DHS Uniform concentrtion up to sorent rekthrough cpcity from low to high oiling point HS-SPME Non-uniform concentrtion rte ue to hesion competition Concentrtion Rte 5 to 50-fol higher thn the sttic HS metho 2 to 5-fol higher thn the sttic HS metho Fig. 1 Scheme of Principles of DHS n SPME Methos 2. Experiment 2-1. Regents A stnr smple mixture consisting of 50 types of voltile sustnces ws issolve in cetone, n then juste to concentrtion of 0 ng/μl. As n internl stnr sustnce, 0 ng/μl of 1,1,1,3,3,3-hexfluoro-2-propnol ws use. Mouse plsm ws use for spike-n-recovery testing, n for ctul smple nlysis, IL- knockout mouse plsm ws use. This is use s n ge-relte Crohn's isese chronic inflmmtion moel, n loo plsm ws collecte from IL- knockout mice (N=6), consisting of one 8-week ol group with minor inflmmtion n 16-week ol group with significntly vnce inflmmtion. For the control group, 8-week ol CBL/6J wil-type mice were use Anlyticl Smple Preprtion Metho For nlysis of the stnr mixture of voltile compouns, 1 ml of phosphte-uffere sline solution n 1.4 g of potssium cronte were e to 20-mL vil. Then, 1 μl ech of the stnr mix- ture of voltile compouns n the internl stnr sustnce were e. In the mouse plsm nlysis, 900 μl of phosphte uffer sline solution n 1.4 g of potssium cronte were e to 20 ml vil. Then, 0 μl of mouse plsm ws e. To this, 1 μl of the internl stnr solution ws e. The prepre smple ws immeitely sele with vil crimp cp. For the septum, 20-mm imeter silicone/ptfe high-temperture sel ws use SPME, DHS-GC-MS Anlyticl Conitions In the HS-SPME extrction, the vil ws first wrme t 50 C in wter th for minutes to equilirte. Following equilirtion, DVB/CAR/PDMS fier (2 cm 50/30 μm, Supelco) ws expose for 5 minutes to the gs phse in the vil for extrction of the voltile components. After the extrction opertion, therml esorption ws conucte y exposing the fier in the inlet for 2 minutes. The injection unit temperture ws set to 280 C for splitless injection. The DHS-GC-MS nlyticl conitions re shown in Tle 1. For the scn/sim metho, the Smrt SIM metho optimiztion softwre feture ws use to optimize the well time. 2

3 Tle 1 Anlyticl Conitions Hespce Smpler GC-MS : HS-20Trp : GCMS-TQ8030 HS-20 Moe Vil wrming Vil stirring Vil pressuriztion time Lo time Injection time Neele flsh time Smple line temperture Trp tuing Wrming time Numer of extrctions Pressure equilirtion time Lo equilirtion time Therml esorption temperture Trnsfer line temperture Trp cooling temperture Trp witing temperture Dry purge time GC cycle time : Trp : 50 C : ON (3) : 2 min : 1 min : 2 min : 5 min : 0 C : Tenx GR (50 mg, mesh) : min : 5 : 0.1 min : 0.1 min : 280 C : 0 C : C : 25 C : min : 60 min GC MS Column Column oven temperture Injection moe Crrier gs Control moe APC1 APC3 Interfce temperture Ion source temperture Mesurement moe Scn event time Scn mss rnge SIM event time : InertCp 5MS/NP (0.25 mm 30 m, 1 μm) InertCp WAX-HT (0.25 mm 30 m, 0.25 μm) : 50 C (3 min) 5 C /min 230 C (1 min) : Split (1:) High-pressure injection 360 kp, 2 min : Helium gs : Liner velocity 30 cm/sec : 0 kp : 65 kp : 230 C : 230 C : Scn/SIM : 0.1 sec : m/z : 0.2 sec 3. Results 3-1. Comprtive Results Using SPME n DHS Methos The HS-SPME metho is sttic extrction metho se on the istriution equilirium of ech phse, n the profile of the voltile components tht exhiit strong mutul interction with the extrction fier is emphsize. On the other hn, the DHS metho relies on ctive purging of the gs phse, n ecuse the voltile components re collecte in the sorent, voltile com- ponents cn e efficiently extrcte n concentrte. To verify this, we compre the extrction methos using mixe stnr smple consisting of voltile sustnces, n exmine the ifferences in the otine voltile sustnce profiles. The nlyticl results re summrize in Fig. 2. Fig. 2 Comprison of DHS n HS-SPME Methos Blck: DHS Metho, White: HS-SPME Metho 3

4 The nlyticl results inicte tht ll of the voltile components were etecte y the DHS metho, wheres y the HS-SPME metho, 1-Propnol, 2-Butnol, 2-Methyl-1-propnol, 1-Penten-3-ol, 2-Pentnone, 2-Methylpropnl, 3-Methylutnl, 2-Methylutnl, n 2-Pentnl were not etecte. Furthermore, the size of the re vlues for 3-Methyl-1-utnol, 4-Methyl-2-pentnol n 2-Penten-1-ol were out one-tenth those otine using the DHS metho. However, the re vlues for the voltile components incluing 2-Ethyl-1-hexnol n 1-Octen-3-one, etc. were comprle using the DHS n HS-SPME methos. A comprison of the men vlues using ech metho inicte 8 % for the DHS metho n 20 % for the HS-SPME metho. Therefore, the overll results inicte tht using the DHS metho, vriety of voltile components, incluing lcohols, etc., which prove ifficult to etect using the HS-SPME metho, cn e etecte with high sensitivity Evlution Results for DHS Metho Using Stnr Voltile Component Mixture Next, we conucte vlition of the DHS-GC-MS nlysis using voltile component stnr mixture. For the vlition, six criteri items were verifie, incluing linerity, R2, LOD, vlue ner the LOD, intry fluctution, n spike-n-recovery testing. Generlly, the LOD is specifie s concentrtion tht provies n S/N rtio of 3, ut using DHS-GC-MS, when lnk smple such s toluene ws use, there were voltile sustnces for which n S/N rtio greter thn 3 ws otine. Therefore, in this reserch, we use the clcultion formul, LOD = 3.3 SD/slope, se on the stnr evition of the quntittion vlues n the clirtion curve slope, s stipulte y IUPAC. The vlue ws clculte se on the nlyticl results corresponing to the voltile component mixture stnr concentrtion nerest the LOD mong 0, 0.1, 0.5, 1,, 25, 50, n 0 ng/ml use to generte the clirtion curve. The spike-n-recovery test ws conucte y spiking mouse plsm with 0 μl of the voltile component stnr mixture. The vlition results re shown in Fig. 3 n Tle 2. 0 ng/ml 50 ng/ml 25 ng/ml ng/ml 1 ng/ml 0 ng/ml 50 ng/ml 25 ng/ml ng/ml 1 ng/ml 0 ng/ml 50 ng/ml 25 ng/ml ng/ml 1 ng/ml 4 Fig. 3 Totl Ion Current Chromtogrms of Voltile Component Stnr Mixture A: 7 to 16 min, B: 16 to 25 min, C: 25 to 34 min

5 Tle 2 DHS-GC-MS Vlition Results Alknes Heptne 2,4-Dimethyl-1-heptene Alcohols 1-Propnol 2-Butnol 2-Methyl-1-propnol 1-Butnol 1-Penten-3-ol 3-Methyl-1-utnol 4-Methyl-2-pentnol 1-Pentnol 2-Penten-1-ol 1-Octen-3-ol 1-Hexnol 1-Heptnol 2-Ethyl-1-hexnol 1-Nonen-4-ol 1-Octnol 2-Octen-1-ol Benzyl lcohol Ketones 2-Pentnone 1-Octen-3-one 2-Octnone 3-Octen-2-one Alehyes 2-Methylpropnl Butnl 3-Methylutnl 2-Methylutnl 2-Butenl Pentnl 2-Methyl-2-utenl 2-Pentenl Hexnl 2-Hexenl Heptnl 2-Heptenl Octnl 2,4-Heptienl 2-Octenl Nonnl 2,4-Octienl 2-Nonenl Decnl 2,4-Nonienl 2,4-Decienl Benzlehye Compoun Trget m/z Slope Intercept R Liner (ng/ml) LOD (ng/ml) c c c c (%)* intry (n=3) (50 ng/ml) Averge (%) (%) Recovery (25 ng/ml, n=3) 5

6 Compoun Trget m/z Slope Intercept R 2 Liner (ng/ml) LOD (ng/ml) (%)* (50 ng/ml) intry (n=3) Recovery (25 ng/ml, n=3) Averge (%) (%) Others 2,5-Dimethylfurn Toluene n-Butylfurn Pentylfurn Styrene * vlue of voltile stnr solution sustnce mixture corresponing to LOD-closest concentrtion : 0.1 ng/ml, : 0.5 ng/ml, c:1 ng/ml, : ng/ml As shown in Fig. 3, y pplying the DHS metho, etection over wie rnge ws possile with 1 ng/ml mixe stnr solution of voltile sustnces. Also, y conucting SIM nlysis of the trget m/z of ech of the voltile sustnces shown in Tle 2, the etection sensitivity tht ws low for lcohols otine using the HS-SPME metho ws elevte to sensitivity comprle to tht otine for lehyes. Also, vlues in the vicinity of the LOD yiele ifferent results epening on the compoun, suggesting the existence of voltile compouns with goo etection repetility notwithstning low LOD, s well s voltile compouns isplying low repetility. The intry vrition vlues for the voltile sustnces were less thn % in ll cses except for 2-Nonenl, Decienl, 2,4-Nonienl n 2,4-Decienl, n in the spike-n-recovery test, except for 2-Methyl-1-propnol, goo results were otine, with vlues t less thn %. Further, s for the verge recovery, the effect of contminnts in the iologicl smple coul not e confirme. The DHS metho, unlike the HS-SPME metho, permits the efficient migrtion of voltile components towr the sorent y forcily purging the gs phse. Therefore, s voltile, low-moleculr-weight components re lso collecte, overll etection sensitivity is improve. The results of this vlition strongly suggest tht vriety of voltile components cn e etecte with high sensitivity using the DHS-GC-MS metho Bloo Plsm Mesurement Results using DHS Lstly, we conucte DHS-GC-MS nlysis of the voltile components in the loo plsm of IL- knockout mice s vivo smples. The IL- knockout mouse is moel mouse for Crohn's isese, chronic inflmmtory owel isese tht cuses gstrointestinl inflmmtion. As smples, the plsms of mouse group with mil egree n rely noticele enteritis, n mouse group with significnt egree of inflmmtion were use. (The inflmmtion egree ws etermine y issection.) As control, wil-type mouse plsm ws use. The otine results were etermine s reltive re vlues ivie y the reltive re vlue of the internl stnr sustnce. As for the nlyticl results, of the 40 voltile sustnces tht were etecte, compouns showe significnt ifference etween smples (Tle 3). Alcohols lso were etecte in the plsm smples, while 2,4-Dimethyl-1-heptene ws etecte only in the isese moel. In ition, since oth Scn nlysis n SIM nlysis cn e conucte using Scn/SIM moe, qulittive nlysis of the voltile components using the NIST lirry ws lso possile. From the ove, it ws emonstrte tht wie rnge of voltile loo components, incluing lcohols, cn e nlyze y pplying DHS-GC-MS. Tle 3 Voltile Components Present in IL- Knockout Mouse Plsm Compoun Control Averge reltive re vlue ± SD (N=6) low inflmmtion, IL high inflmmtion, IL Butnl* 8.0 ± 2.9 E ± 0.4 E ± 0.8 E-01 1-Propnol 3.6 ± 0.7 E ± 0.5 E ± 0.9 E-01 2-Butnol* 3.2 ± 0.4 E ± 2.1 E ± 0.9 E-01 2-Pentnone* ± 1.2 E ± 0.6 E ± 0.5 E-01 Heptne* 3.5 ± 0.4 E ± 0.5 E ± 0.3 E-01 1-Butnol 1.3 ± 0.4 E ± 0.1 E ± 0.3 E+00 Pentnl 3.5 ± 1.8 E ± 0.8 E ± 1.1 E-01 1-Penten-3-ol 5.0 ± 3.4 E ± 1.8 E ± 2.9 E-01 3-Methyl-1-utnol* 1.5 ± 0.6 E ± 0.6 E-01 ± 0.4 E-01 2-Pentenl 4.7 ± 3.4 E ± 2.7 E ± 1.8 E-02 4-Methyl-2-pentnol 1.9 ± 2.7 E ± 3.2 E-02 ± 2.1 E-02 Toluene* 6.4 ± 0.7 E ± 0.5 E ± 0.5 E+01 1-Pentnol 9.5 ± 4.4 E ± 1.1 E ± 0.8 E-01 6

7 Compoun Control Averge reltive re vlue ± SD (N=6) low inflmmtion, IL high inflmmtion, IL Hexnl* 2.8 ± 6.2 E ± 1.2 E ± 1.3 E-01 2-Penten-1-ol 0.5 ± 1.1 E ± 1.8 E ± 0.2 E-01 2,4-Dimethyl-1-heptene* ± 0.9 E ± 1.1 E-01 1-Hexnol 1.2 ± 0.3 E ± 0.3 E ± 0.5 E-01 2-n-Butylfurn* 0.6 ± 0.8 E ± 0.9 E ± 0.5 E-02 Heptnl 0.5 ± 1.2 E ± 1.9 E-02 ± 1.6 E-02 Styrene 2.8 ± 1.2 E ± 1.1 E ± 1.6 E-01 1-Octen-3-one 0.9 ± 0.6 E ± 0.6 E ± 0.7 E-01 1-Heptnol 0.8 ± 0.7 E ± 0.5 E ± 0.7 E-01 2-Pentylfurn 5.8 ± 1.1 E ± 0.7 E ± 1.5 E-02 2-Octnone 1.5 ± 0.4 E ± 0.5 E ± 0.3 E-01 Octnl 2.5 ± 1.0 E ± 1.0 E ± 1.3 E-01 Benzlehye 1.4 ± 0.1 E ± 0.1 E ± 0.1 E+01 2-Ethyl-1-hexnol 2.3 ± 0.6 E ± 0.5 E ± 0.7 E+01 3-Octen-2-one 1.5 ± E-01 ± 1.1 E ± 2.8 E-01 1-Octnol 2.2 ± E ± 0.3 E ± 0.6 E-01 2-Octen-1-ol 5.8 ± 1.5 E ± 2.1 E ± 2.6 E-01 Nonnl 3.7 ± 0.8 E ± 3.0 E ± 0.9 E-01 2,4-Octienl* 1.6 ± 1.6 E ± 0.7 E ± 0.9 E-02 Benzyl lcohol 1.2 ± 0.1 E ± 0.1 E ± 0.2 E+03 Decnl 1.8 ± 0.7 E ± 0.3 E ± 0.9 E-01 2,4-Nonienl 9.6 ± 3.8 E ± 3.5 E ± 0.4 E-01 Acetone_NIST* 2.1 ± 0.3 E ± 0.6 E ± 0.2 E+02 2-Propnol_NIST* 9.1 ± 1.1 E ± 0.9 E ± 0.8 E+03 3-Methyl-2-utnol_NIST* ± 0.5 E ± 0.5 E ± 0.5 E+00 2-Methyl-2-utnol_NIST* 5.1 ± 0.8 E ± 1.0 E ± 0.6 E+03 Unknown_NIST* 8.0 ± 1.1 E ± 0.9 E ± 1.5 E+01 * A significnt ifference (p<0.05) ws confirme in t lest one set mong the three groups using the t-test. 4. Summry Use of DHS-GC-MS with the HS-20 trp enle nlysis of trce level loo components. Using stnr mixture of voltile components, results were compre with those otine using the HS-SPME metho. The use of DHS permits etection of wie rnge of voltile components, incluing lcohols, with high sensitivity. Furthermore, the vlition results emonstrte the etection of ll the voltile compouns t ng levels. Also, the results of mouse plsm nlysis inicte the etection of voltile components incluing lcohols, emonstrting tht mesurement of trce-level voltile components is possile. These results emonstrte tht this system offers superior sensitivity to tht otine using SMPE in the mesurement of voltile components. This technique is suggeste for use in profiling voltile compouns in clinicl reserch. 5. Acknowlegment The IL- knockout mouse plsm ws kinly provie y Associte Professor Msru Yoshi n Lecturer Shin Nishiumi, Grute School of Meicine, Koe University. References Multi-Component Profiling of Trce Voltiles in Bloo y Gs Chromtogrphy/Mss Spectrometry with Dynmic Hespce Extrction S Kkut, T Ymshit, S Nishiumi, M Yoshi, E Fukuski, T Bm Mss Spectrometry 20 Vol.4 (1), A0034 A0034 7

Hespce Smpler HS-20Series A Revolutionry System Aime t Performnce n Ese of Use The HS-20 Series is the optiml solution for voltile component nlysis.

In ition, n oven with mximum temperture of 300 C enles nlysis of high-oiling compouns. User-Frienly Design Esily plce smples in the try with the user-frienly esign.

8 Hespce Smpler HS-20Series A Revolutionry System Aime t Performnce n Ese of Use The HS-20 Series is the optiml solution for voltile component nlysis. Its superior performnce n user-frienly esign support ll types of nlyses, from reserch to qulity control. Excellent Performnce High reprouciility n low crryover ensure relile quntittion. In ition, n oven with mximum temperture of 300 C enles nlysis of high-oiling compouns. User-Frienly Design Esily plce smples in the try with the user-frienly esign. Also, the neele, smple loop, trp, n other consumles cn esily e replce from the top of the instrument. Excellent Expnility With the trp moel, concentrting the hespce gs enles the nlysis of ultr-trce components, such s gses relese from prts n mterils. The optionl rcoe reer enles smples to e controlle vi chromtogrphy t system. Brochure: C146-E209 Triple Qurupole Gs Chromtogrph Mss Spectrometer Finlly, triple qurupole GCMS Smrt enough for everyy use in your lortory. The Shimzu GCMS-TQ8040 is the first triple qurupole with Smrt Prouctivity for high efficiency smple throughput, Smrt Opertion for quick n esy metho evelopment, n Smrt Performnce for low etection limits n Scn/MRM. These three smrt technologies contriute to Smrt MRM, n provie the most ccurte, cost-effective, n esy-to-use triple qurupole GCMS you hve ever imgine. Retention time synchronize MRM provies simultneous sensitivity n precision for hunres of compouns in one run Smrt MRM optimizes nlysis of 400+ compouns in single cquisition with mximum sensitivity Reuce owntimes with the Twin Line configurtion MS system MRM Optimiztion Tool to optimize MRM trnsitions utomticlly Smrt Dtse Series with fully optimize trnsitions for hunres of compouns Smrt MRM for utomtic metho cretion in single step The ptente ion source esign n uniform temperture prevent ctive spots n oost sensitivity The OFF-AXIS ion optics eliminte chemicl noise n lower etection limits High-sensitivity nlysis even in single GC-MS moe ( 1,000) (,000,000) > > MRM Totl Ion Current Chromtogrm (TIC) of MRM mesurement for Metolites in Stnr Humn Plsm 1.0 ( 1,000) Vlproic ci-tms ( 1,000) 248.> > Scn MRM Scn 3-Aminoisoutyric ci-3tms Comprison of MRM n Scn Mss Chromtogrms for Metolites in Stnr Humn Plsm 1.0 ( 1,000) min Brochure: C146-E251 First Eition: June, 20 For Reserch Use Only. Not for use in ignostic proceures. The content of this puliction shll not e reprouce, ltere or sol for ny commercil purpose without the written pprovl of Shimzu. The informtion contine herein is provie to you "s is" without wrrnty of ny kin incluing without limittion wrrnties s to its ccurcy or completeness. Shimzu oes not ssume ny responsiility or liility for ny mge, whether irect or inirect, relting to the use of this puliction. This puliction is se upon the informtion ville to Shimzu on or efore the te of puliction, n suject to chnge without notice. Shimzu Corportion, 20

METHOD 4010 SCREENING FOR PENTACHLOROPHENOL BY IMMUNOASSAY

METHOD 4010 SCREENING FOR PENTACHLOROPHENOL BY IMMUNOASSAY 1.0 SCOPE AND APPLICATION 1.1 Method 4010 is procedure for screening solids such s soils, sludges, nd queous medi such s wste wter nd lechtes