~ p O S ~

11. New Mass Spectrometric Methods

Negative Ion Mass Spectrometry

R = reagent gas M = substrate molecule

H. Brandenberger

I

e-

---*R

Gerichtschemische Abteilung der Universit~it, ZiirichbergstraBe 8, CH-8028 Z/irich, Switzerland

k

pos. CI

Negativionen-Massenspektrometrie

R + + M--+[MR] +, [MH] + Mainly cluster cations + Electron attachment e-* + M ~ M ~ .

neg. CI (1) Mass spectrometry (MS) by negative chemical ionization (CI) can be carried out by several basically different reaction mechanisms. While positive CI requires high source pressure (over 10- ~Torr), the negative CI modes 1 - 3 (Scheme I) work very well in the low pressure range between 10-3 and 10 -2 Torr. Negative CI by electron attachment (mode 1) requires reagent gases such as CH~ or noble gases which yield - on electron impact (EI) - mainly positive ions and secondary low-energy electrons. It should be used, especially in combination with chromatographic techniques, for the trace detection of compounds possessing high electron affinity (electron capture detector of the future). In addition, electron attachment MS can also be an extremely helpful tool in structural elucidations. For the analysis of compounds with low electron affinity, the negative CI mechanisms 2 - 5 (for low pressure work only modes 2 and 3) have to be used. They require reagent gases convertible by EI to negative reagent ions such as O - (from COz or N~O), [NO]- (from N20), F - or C1- (from Freons or CH2C12). The charge transfer from such anions to the substrate can be quantitatively as effective as positive ion formation by EI or CI.

NET

.O"J SCr 72

101 B~gS-X100"/.

Fff:OQ~46

IO0>'~L:~B26EI

e- = primary electrons, high energy e-* = secondary electrons, near thermal energy

[ M - H][ M - X]-

or neg. CI (2)

R-

+ M ~ M-

Charge exchange

neg. CI (3)

R-

+ M ~ [ M - H]-

Proton abstraction

neg. CI (4)

R-

+ M ~ [ M - H + R]-

Substitution

neg. CI (5)

R-

+ M-+[MR]-

Cluster anions

source - high for pos. CI and neg. CI mode 1, pressure - low or high for CI modes 1 - 3, must be: - preferably high for CI mode 4. Scheme I. Possibilities for negative chemical ionization Negative CI spectra of some biologically or toxicologically active compounds, obtained by different ionization modes, will be compared. It will be shown that in structural analysis, negative ion MS - either with CI, desorption or sputtering techniques is an ideal complement to positive MS by EI.

TIC:Sgg040

X20

often with dissociation

~6H5 Xl

~.

~H3

METHADONE

CH3CH2CO~--CH2CHN(CH3)2

l,t

,

,

,,

[

=

309

Reagent

C6H5

,tL.,

Mr

G a s CH/,

~8 Fig. 1

252

"~-' ~SO" ~ ' MET

.02 ~

C14L:)Q~ .100 ~

't~

'120' ~ . i O '

100 B~94XIO0"/.

RT:O~=44

501 BI44gX$O0"4

69

'1SO' "leo'

for=09149

'ao<~ Pao'

'a,~

~6'

~>'

~oo'

Dual-MS of methadone '

tO0~L~O1:P'2~ T ] C : 3 0 7 2 0 0

100-/~t~401B0 T]C='J6"~4~40

H

iso

141

Hydroxypentobarbital

0

o

Mr= 242

c.- c.= c. c.= 197

45

...I .,tL ..~" L-.,....J, __t

,

.

,LL

CH=

[

213

Fig. 2 Dual-MS of hydroxypentobarbital

'160' '~L=~ ~oo' ~2o' ~4o' bso" Iso' ~,o' '1oo' l~d 14o .OK> ~ ~ BI4~OXtO0"/. IRT=O~zE>O t OOP~ t t 3 0 q g 6 T | C: 1 : 7 4 4 B ~

C101~

. 0 0 SCINt 121 B I l t ~ t 0 0 " / .

RT:O',2=58

'aso"

boo'

CH4, 3 9 10 a torr

~

a

a

209 i i ' [50 ' L~O ' 'I(XJ 'IL:~' '140' ~ 'tEId ~o ~'~0' ~40' =L:~O' ~980' ~300' C1018~' . 0 0 ~ tL:~ B = l I 6 X l O 0 " 4 w r = o ~ 1 5 6 10o',,.~t68960 TIC=L:W39616

634

'

Tributylphosphate, Mr = 266

57 /

1

'

tO0"/'~41Bl~31B T I C : t 1 9 0 6 0 4 8

99

iL

Reagent Gas CH4

2~

156

~o' C14~

O~

Fig. 3 Dual-MS of tributylphosphate

12. Methoden der Orogenanalyse

El

~ f f ~ O $ ~

I

Cl

I

I I[I imL '

~ 1

I

'

a,~ o

I

Conventional positive EI-MS is hardly affected by the presence of reagent gases at pressures below 10-2Torr (Scheme II). We have therefore combined negative CI-MS at J0-3 to 10-2 Torr with positive EI-MS to obtain an interesting quasi-simultaneous dual-MS-system which characterizes an unknown 1. by its conventional positive ion spectrum obtained by hard EI, 2. by an additional low-pressure negative CI spectrum yielding complementary structural information, and 3. by indication of the molecular mass, usually given by the softer CI method. This dual-MS-system is now used routinely in our laboratory to solve toxicological and forensic problems. Figures 1 - 3 show the quasi-simultaneous recordings of the positive EI and negative CI spectra of 3 exogenous compounds extracted from urine and separated by GC: methadone (a drug), hydroxypentobarbital (a drug metabolite) and tributylphosphate (a plasticizer).

Scheme II. Pressure dependence of positive and negative ionization modes

Fresenius Z Anal Chem (1984) 317 : 6 3 4 - 635 9 Springer-Verlag 1984

Symposium 12: Methods of Drug Analysis Symposium 12: Methoden der Drogenanalyse The Drug Situation in Europe and its Analytical Implications R. L. Williams Metropolitan Police Forensic Science Laboratory, 109 Lambeth Road, London, SE1 7LP, UK Die Drogensituation in Europa und ihre analylischen Konsequenzen Although it is almost a platitude to assert that there is a growing drugs problem throughout Europe, it is surprisingly difficult to collect information on which to make quantitative comparisons between countries. There appears to be no systematic collection of data centrally, e.g. through UNESCO or INTERPOL, and the problems is exacerbated not only by the wide variety of drugs that are misused but also by the lack of clear definitions of what exactly are the data that are being recorded.. However, assessments can be made. For example the following figures have been quoted for some major seizures of heroin (kg). France Germany Sweden UK

1980 47.7 241.9 1.5 51.8

1981 42.6 89.6 8.1 89.4

1982 67.0 185.4 1.5 100.7 (source INTERPOL)

but a second reference gives for 1982: Yugoslavia 301 ; Germany 240; Italy 233; Netherlands 91. The discrepancy in the value for Germany typifies the uncertainty involved with such assessments. These figures are only a reflection of the actual levels as modified by the effectiveness and activity of the enforcement agencies and by the efficiency of the data collecting system. For example in the UK, police forces deal with internal seizures and these are not reported in the figures cited above which are seizures at points of entry made by Customs. The analyses are carried out by the Laboratory of the Government Chemist (LGC) and it is an indication of the chaotic state of drugs intelligence that the LGC data for the years 1980, 1981 and 1982 are 38, 87 and 183kg respectively ! Another means of evaluating the problem is to examine figures for drugs analyses carried out by the forensic science laboratory/ies of the country in question. For example the Swedish National Laboratory received 4,706 cases in 1981 and 4,102 in 1982 whereas the data for England and Wales (7 laboratories) are as follows: 1980, 19,443; 1981, 21,081; 1982, 24,481 to which the London (Metropolitan Police) Laboratory contributed on average over 40 %. Not only do these data suffer from the defects mentioned earlier but they represent "possession of drugs" cases and hence cover quantities ranging from a few mg to kg. Nonetheless despite their deficiencies the growth trends are well established. Details of some specific drugs are as follows. 635