827 



19* 



BYPD £T AL 



MS uilng (lie conditions In this audy eave (M + NH4)* at m/i 

 13S. (M + NH. - H,0)- »l m/z 320, an<S the gjucaronidc 

 iVasmcnt J« m/r 194 tint malchod the rcpoittd btliavlcr for tills 

 compound (17). T-<ro nitrofcn-containinj glucuronide», 8-hy- 

 •Iruxyquinolinc glucuronid« end <^«niinophflnyl gluwjronidc, 

 »»vc very ilrong (M + H)' iont M m/x 323 And 2«4, r««p«cl.iv«ly. 



I'he »mounts of e»ch mcaiured tr.etibolit* excreted in « 2*- 

 hf urine sample an: lisw<l In tAbk 1 for tlie 1 1 unokfift The 

 variability of thtse ab«oiule «mo«inU in temu of the cotffioient 

 of •aruuion ra-Tics from 15% for tJimethylcoiiniDC to 70% (or 

 nicotine gjucuionide conjugate. The diitribtitsoi! of ihe major 

 ntctahotitcs (nicxitine, cotlnlne, aad (ranJ-S'-hydroiycoiioiue) 

 tx:i»<en ;he free and oonjuiztcd fotnu is shown in figutr 2 for 

 trie 1 1 jmokers. Plstite 2 Ultisvatcs thit free iranj-i' -hydroxy- 

 coiiniac «M unlltormiy ihe most aOuiuiani nictatottte tneasured 

 !iir all imnkrm end looruntcd, ca »vengc, for 33 » of the total 

 metabolitcj d«cetcd. Tlic pcxoeat of each metabolite «3 the 

 fluCMrnaide oor.juealo v«<-i8d « great dwd for nicotine (0 to M%) 

 and cotinLn€ (4 to 76«) and Mmswtual 1«1» for (nww-S'-hydrox- 

 yaJtia'_ie(lOto30%). 



la order to compare the relative dutribuiioa of .-neuboUtet 

 iunoo£ smokcn. the amouDt of each raeaboltte was ixmyated 

 10 nitxjlinc (ajutvalenti by muWplylns by tbe tasio of tbs molic- 

 ulai weighu of nicotine to the metabolite. Theie roultj are also 

 listed in table 1 as percent of the total arnotjot dstcrtaiflcd. These 

 ivert^M at the bottom of tabic I are plotted in fig. 3 in cr^cr of 

 docrcaiiog abundajioe, witt encr ban to indicate the rtandwd 

 dcviaiton amon^ the 1 1 mokers. From this tiata, ^iK prtjportioti 

 ofmeutwliUa cxctcokI a gUjctaoaW* conjugates can be deter- 

 mined. Total 0ucuronlde coi;)U8at« accooBted for 15 to 37% 

 of all tncisured raeiaboUies, with aa avcraee of 2?S (br the 1 i 

 smokers. 



.Mthough it hoj not baco demcoatralcd tiuJ all of the njaxins 

 flbeotbed while eaiotdBg caa bo qtantftative}/ recovered in urine 

 u nlcotme and itszaMabotit**, It U of Interttt lo datermigcvrhat 

 pQilioo of FTC nicotine yidd cifl be rwxwsred in urina. T«ble 

 2 lists tie FTC nicotine yield for each tmnker and the total 

 aicoiins CQuivalccts detennined in iMs R'jdy. The narahe* of 

 dgaretles coajuoted the «isy of taioc colkctioti t^sged ftccn 12 

 to 80. and the total FTC nieotitie f'M far thctc cigarettes varied 

 from 113 10 442 mg, Tibk 2 ahows nicotine otttpui in these 

 snsotefs' urine* raagsd from a ratio of 0^5 lo 1.44 of the FTC 

 yielda, with an aNOtage of 0.96 ^ 0J9. 



DtMouioa 



'litis study confirms curlier obsetvailons that nicotine can Ix 

 ractaboli7«d to RlucarciUde conjugaics in humaas (6-?). We 

 prejflni data that deraoaiti^itc only oicutine, tjjtinine, tad iran3- 

 3' -liydrosyootitiine arc excreted In smoker"! urine u glacu tunide 

 con)u^tw und ooiutituta J9* of the totil mrfebolile* detected 

 in urine for the 11 tmoV«rt cMiniocd in tbi« itudy. Using a 

 therroa-oray LC/M.S techruque developed in our laborjlcy that 

 p<.Tnit.<lheamultanfousdetennin«iion nf nicotine a4ul t7oriU 

 free mctobolites tt\ human urine (13). v« have dctcrmiiwri that 

 none of the other free metabolites that aoocar in imokei" tirine 

 aie cicr.-tcd as gUicuronide coD'ugates. Of the numcruoj fnx 

 melabollt■.:^ of nicotine n.-ported in tJie literature, only dcmrihyl- 

 colirtine, nicotine-W .oxide, and cotininc-A'-oiiidc were cxcrctDd 

 in nicasurahli; ouanlitie* (detection limi's ;0 to 2W ng/ml). 



!n coir.pannon. Cunall c a-' {(>'■ who itudicd eig.ht jrnolcers, 

 roiiml J tiighc.' pfOi>ortinn r.f the taaioi mctatwims ev.tncd m 





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