Direct mixture analysis of surfactants by combined field desorption

1458

Anal. Chem. 1902, 5 4 , 1458-1466

Direct Mixture Analysis of Surfactants by Combined Field Desorption/Collisionally Activated Dissociation Mass Spectrometry with Simultaneous Ion Detection Raymund Weber and Karsten Levsen" Institut fur Physikallsche Chemie, Wegelerstrasse 12, 0-5300 Bonn, Federal Republic of Germany

Gerard J. Louter, A. J. Henk Boerboom, and Johan Haverkamp" FOM-Institute for Atomic and Molecular Physics, Kruisaan 407, 1098 *SJAmsterdam, The Netherlands

The combination of field desorption (FD) and collisionally activated dissociation (CAD) has been used to analyze mixtures of cationic, anionic, and neutral surfactants wtthout prior Separation of the components. For this study a specially designed tandem mass spectrometer with simultaneous Ion detection was employed which allows a complete CAD spectrum to be recorded with 5 pg of sample. The FDICAD spectra allow a straightforward and unambiguous structure elucidation (including the determination of the length and branching of the alkyl chains) of cationic and anionic surfactants while the interpretation of the FD/CAD spectra of the nonionic surfactants Is more complex.

Surfactants are organic compounds that when added to a liquid change the interfacial properties of that liquid. They are used as wetting, foaming, dispersing, emulsifying, and penetrating agents and are the major organic constituents of detergents. Surfactants are mostly classified by the nature of their ionic charges. Thus one distinguishes between three types of surfactants: (a) cationic (such as quaternary ammonium salts), (b) nonionic (formed, e.g., by condensation reactions between ethylene oxide and fatty alcohols or alkylphenols), and (c) anionic (e.g., alkylbenzenesulfonates or alkylsulfonates). Surfactants are typically manufactured as a mixture of homologous compounds, the Constituentsof which differ in the length of the alkyl or ethoxylate chain. As the constitution of the mixture strongly influences its physicochemical properties, adequate analytical methods are needed. Furthermore the release of surfactants to the environment (in particular to surface water) has required the development of sensitive analytical methods for their determination at trace levels. The various methods developed and employed up to date have been reviewed recently (1). The most common procedure for the determination of cationic and anionic surfactants is by colorimetry (2,3).Although simple, these methods are neither very specific nor very sensitive. Moreover, most of the other analytical techniques proposed so far do not allow the determination of the exact constitution, in particular the alkyl moiety, nor do they permit the determination of the distribution of chain lengths, although it has been reported that the chain length distribution affects considerably the properties of cationic surfactants (4). Recently the determination of alkyl chain distribution of alkylbenzenesulfonates by high-performance LC has been described (5). While organic compounds at trace levels in various sample matrices are most readily identified by combined gas chromatography/mass spectrometry (GC/MS), this method cannot be applied directly to the analysis of surfactants as these compounds are too polar to be amenable either to gas chro0003-2700/82/0354-1458$01.25/0

matography or to conventional electron impact (EI) mass spectrometry. However, Linhart and Wrabetz (4,6)reported pyrolysis GC/MS of cationic surfactants. Moreover, it has been demonstrated by Julia-Dan& and Casanovas (7) that none of the ionic surfactants are sufficiently volatile to be analyzed by E1 mass spectrometry (without prior separation). In recent years a variety of new mass spectrometric ionization techniques have been developed which also allow the analysis of strongly polar compounds (8). In addition, it has been demonstrated that tandem mass spectrometry, now commonly referred to as mass spectrometry/mass spectrometry (MS/MS) (9-11) can be used for direct mass spectrometric mixture analysis. We wish to report here that a combination of field desorption (FD) (12) and CAD mass spectrometry (13,141can be used successfully for a direct mixture analysis of cationic, nonionic, and anionic surfactants. This approach has been used previously by Weber et al. for the analysis of thermally labile compounds (15, 16). With this technique a major experimental problem arises from the fact that the FD method often leads to strongly fluctuating, short lasting ion currents and that the intensity of the CAD fragments may be very low. For the present study our newly developed tandem mass spectrometer was used. It has a very high transmission for CAD fragments and employs simultaneous ion detection (17). This allows the study of short lasting ionization phenomena and the detection of extremely weak currents (1ion per 250 s) (18).

EXPERIMENTAL SECTION The tandem mass spectrometer used for all measurementshas been described previously by Louter et al. (17). Preselection of the ions to be investigated is performed in the first stage of the mass spectrometer, which has a conventional sector magnet. A collision cell is mounted at the site of the detector slit followed by a postacceleration stage (-20 kV) in which the precursor and fragment ions are accelerated to a total translational energy of maximally 26 kV. For this purpose the first stage of the instrument is floated at high voltage with respect to the second stage. Mass analysis of the CAD fragments is performed with a second magnet. A system of three electric lenses and one magnetic quadrupole lens allows one to focus the ions onto a double channeltron electron multiplier array (CEMA) detector of 75 mm diameter and to vary the simultaneouslydetected mass range from 1:1.06 to 1:4. A decreased dispersion implies, however, also a decreased resolution. The CEMA is followed by a phosphor screen. The signal is guided out of the vacuum envelope by a fiber-optic slab and recorded by using a Reticon photodiode array with 1024 channels. This system allows the simultaneousdetection of a mass spectrum. The transmission from the collision cell to the CEMA ranges from 60 to 100%. Data storage and processing are done by a PDP 11/70 computer, which performs the following operations: background subtraction, correction for sensitivity variation along the CEMA, and mass scale calibration. The 0 1982 American Chemical Soclety

ANALYTICAL CHEMISTRY, VOL. 54, NO. 9, AUGUST 1982

1459

X6.67 i

Figure 1. Fieid desorption/collisionaily activated dissociation (FD/CAD) spectrum of (CH,),N+(CBH,,)2CI- (HoeS2617). The cation is the precursor ion. The spectrum has been recorded in three successive mass ranges (see Experimental Section). Overlapping mass ranges have been omitted.

spectra can be either plotted (see Figures 1-9) or printed in tabulated form. The instrument was equipped with a FD source (19). Tungsten wires (10 pm) activated with benzonitrile were used as FD emitters. The emitter was heated by a dc current of 0-18 mA in the case of nonionic surfactants, 20-40 mA for cationic surfactants, and 45-60 mA for anionic surfactants. The potential difference between emitter and counterelectrodewas 10 kV. Helium was used as collision gas; p = 5.3 Pa. The sample was dissolved in methanol or 2-propanol and applied to the FD emitter using the dipping or, for quantitative measurements, the syringe method. Prior to field desorption and floating of the first stage of the mass spectrometer at high potentiall, the position of the emitter was optimized geometrically using the field ionization signal of acetone. For reasonable resolution each CAD spectrum was recorded in three overlapping sections; in the case of anionic surfactants the lower mass range extends from m / z 20 to 80, the medium mass range from m / z 60 to 200, and the upper mass range up to the precursor ion mass. Depending on the precursor ion intensity the CEMA detector was exposed to the ion current for 5-80 s. The relative intensity of the ions within one of these mass ranges depends strongly on the docusing potential of the first electric quadrupole which was adjusted to obtain optimum ion intensity in the central part of the mass range. This leads to a desired enhancement of the fragment intensity relative to that of the precursor. On the other hand, it is not possible to represent the intensities of all CAD fragments relative to a precursor ion or a given fragment ion, as the relative abundance of a given ion within the overlapping region of two mass ranges need not to be identical in each mass range. Thus, if no original spectra are represented the relative fragment abundances are discussed in terms of “low”, “medium”, and ”high” abundance. The surfactant samples were commercial products from Hoechst and Chemische Werke Marl Huls.

RESULTS AND DISCUSSION Cationic Surfactants. Cationic surfactants are quaternary ammonium salts with one or several long alkyl chains as hydrophobic moiety. The FD spectra of small quaternary ammonium salts have been reported previourdy (20-24).They are dominated by the cation (Cat+)and lesu abundant cluster ions, [M, + Cat]’. The latter peaks give information on the anion. This is important iw the nature of the anion influences the properties of the surfactant. Fragment ions are absent or of very low abundance so that the FD spectrum alone does not allow the determination of the structure of the cation. This is, however, possible with combined field desorption and CAD as shown in earlier FD/CAD studies of (usually small) quaternary ammonium salts (25-28). These earlier studies

R R

I

demonstrated that the CAD spectra of tetraalkylammonium cations are dominated by three processes which allow an unambiguous structure assignment (Scheme I): (a) loss of one substituent (alkyl loss); (b) loss of one substituent with concomitant hydrogen transfer (alkane loss); (c) alkyl loss followed by a-cleavage of a second substituent. The cationic surfactants investigated in this study are shown in Table I. They are either tetraalkylammonium or trialkylbenzylammonium salts. For a direct mass spectrometric mixture analysis of these surfactants the first magnet of the tandem mass spectrometer was successively adjusted to pass the various cations, the CAD spectra of which were obtained as described in the Experimental Section. As also explained in that section it is not meaningful to report the relative abundance of the various CAD fragments in the tabulated form. Figure 1shows the CAD spectrum of the cation [ (CH&N(CBH1,)2]+ for three successive mass ranges. This spectrum is typical for all tetraalkylammonium cations. As expected the spectrum is dominated by alkane (octane) loss (process b) which leads to m/z 156 and alkyl loss with consecutive a-cleavage of the second substituent (processes a and c in Scheme I) which gives rise to a fragment at m / z 58. This fragment is typical for dimethyl-substituted cations. In conjunction with the precursor ion mass these two fragments allow the unequivocal determination of the four substituents. Alkyl loss (process b) is not resolved from alkane loss but (if occurring a t all) appears to be of minor importance. This dominance of alkane loss and alkyl loss with subsequent acleavage and the minor importance of alkyl loss in the CAD spectra holds also for all other tetraalkylammonium cations as summarized in Table I. The dimethyldiulkylammonium

1460


114

I

L1 43 h

A

Flgure 2. FD/CAD spectrum of the catlonlc surfactant Dodigen 1490. The catlons (CH3)2N+(C,4H2s)2 and (CH3)2N+(C12H25)(C,8H33) are the precursor

ions.

Figure 3. FD/CAD spectrum of (CH3),N+(C,,H2&(CH2C,H,)CI-.

The cation is the precursor.

cations, [(CH3)2NR1R2]+ give rise to one abundant peak in the upper mass range which results from aikane loss if R' = R2 (i.e., the cations 1,2,4,6), but to two peaks if R1 # R2 (Le., the cations 3,5,7). In the latter case the larger substituent is usually lost preferentially which is in agreement with earlier observations made with small tetraalkylammonium cations (25).Alkyl loss with successive a-cleavage leads to an abundant mlz 58 in all cases which allows the rapid identification of dimethylammonium surfactants. The spectra of the methyltrialkylammonium cations [CH3NR12R2]+are slightly more complex if R1 # R2 (cations 9, 10) as in this case two peaks due to alkane loss are observed in the upper mass range and two peaks due to alkyl loss with subsequent a-cleavage in the medium mass range. These four peaks allow an unambiguous and rapid identification of the cation structure. One trimethylalkylammoniumcation (12) has been studied. Here only one major peak is observed in the spectrum at mlz 58 which may result from both alkane (hexadecane) loss or alkyl (methyl) loss with subsequent a-cleavage of the hexadecyl substituent. While the alkyl loss (process a in Scheme I) is suppressed in methyl- and dimethylammonium cations (vide supra), this process is observed with 12 and leads to m/z 59.

The potency of the FD/CAD method for the analysis of cationic surfactants is illustrated in Figure 2 which shows the CAD spectrum of a cation of m/z 438. The abundant peak at mlz 58 reveals that a dimethylammonium cation is present.

However, in the upper mass range not two but three abundant peaks are observed at m/z 212,240, and 268. As these peaks can only be due to alkane losses (i.e., the loss of three distinct alkyl substituents), the only reasonable explanation is that there are two isobaric precursors at m/z 438,i.e., [(CHJ2N6, and [(CH~)2N(Cl2Hzs)(C16H33)1+, 7. Moreover, (CI~HZ&I+, it is possible to conclude from the intensity ratio of m/z 212, 240,and 268 that 7 is approximately twice as abundant as 6. This example demonstrates that the FD/CAD method also allows the identification of isomeric cationic surfactants. Finally a surfactant has been investigated which consisted of a homologous series of dimethylbertzylalkylammonium cations, [(CH3)2(C6H5CH2)NR]+, Le., the cations 13, 14, 15, 16, and 17, in Table I. The CAD spectrum of 15 is shown in Figure 3 as an example. Apart from the alkane loss and the alkyl loss with subsequent a-cleavage loss of C7HB (which corresponds to the alkane loss) leads to an abundant fragment. The latter process is, in general, less intense than the alkane loss (see Table I). In conjunction with the benzyl ion (mlz 91), which is also observed with high intensity, this process facilitates the structure elucidation of this type of surfactant

(28). So far only the dominant fragments in the CAD spectra of cationic surfactants have been discussed. These dominant peaks allow an unequivocal identification of the structure of the surfactant. However, in all spectra a large number of less abundant fragments is observed, which may in part be helpful


1461

Table I. Investigated Ctdionic Surfactants and Their Main CAD Fragments

mlz compd trade mark

no.

Hoes 2617 Dodigen 1881

1 2

Dodigen

CH,N+;

Hoes 2706

\

-

[CatR2 -

other abund. fragments

[Cat]+ 270 326

156 184

3 54

212'"

382

212

410

240'"

438

24 0

43 8

212'"

368

2 54

396

282'"

254

156a

184

424

282'"

310

184'"

156

452 284

310 58

276

134a

184

58d

91

304

134'"

21 2

58d

91

33 2

134

240'"

58d

91

360

134 a

268

58d

91

388

134a

296

58d

91

[Cat-

[CatR2HI+b R3H]+b

Rl3

a]+

a]+

58 58 58

184

58 58

212

58 58

268

156

'=loHz1

1

i

Dodigen 1383

[Cat -

[Cat R'H]+

CH3N+,

lo '11 12

I '

17 l6

7

184 59

R', R2 = alk.yl substituent (except methyl), R3 = benzyl substituent. '" Dominating RH loss. Loss of an alkyl substituent with consecutive or-cleavage of the second substituent. Loss of a benzyl substituent with consecutive a-cleavage of the second substituent.

to aid the structure detiermination. Thwi in the CAD spectra of the tetraalkylammonium cations a series of weak fragments equidistantly spaced by 14 mass units (CH,) is observed in the higher mass range. This series originates from losses of CnH2n+2 where n ranges from 2 up to the maximum number of carbon atoms of the alkyl substituent as evident from Figures 1 and 2. By simply counting these weak peaks, one can establish the number of carbon atoms of the alkyl chain. Apart from these peakri there are series of weak peaks which are less structure specific. Among these are hydrocarbon ions which originate from the aliphatic substituents ( m / z 39,41, 43,55, 57,69, 71) or from the aromatic Substituent ( m / z 51, 63,65). Furthermore there are series of fragments which may contain a nitrogen atlom (Le., m/z 88, 100, 114, 128, [(CH3)2N=CH(CH2),CH3]+; 84, 98, 112, ..., [(CHa),N= CHCH=CH(CH2),H]'). Anionic Surfactants. Anionic Surfactantscomprise about 80% of all surfactants itnanufactured worldwide. Among the anionics alkylsulfonate3and alkylbenzenesulfonatesplay the ,# ..

most important part. Again these two types of anionic surfactants are present as mixtures of homologous compounds with four and five components. The products investigated are compiled in Table 11. The positive FD spectra of pure sodium sulfonates have been reported earlier (29,30).They are dominated by quasi-molecular ions formed by sodium attachment to the salt [M Na]+, and cluster ions of the general type [M, Na]+ ( n I6) while the molecular ions themselves are less abundant (30). Both M+. and [M + H]+ ions have been observed (30). In the present study the [M + HI+ ion has been selected as the precursor of the CAD spectra. If fragment ions are observed they are of low intensity and not always structure specific. Thus, although FD spectra allow the determination of the molecular weight they are less suited for the elucidation of the structure of sulfonates, in particular when these compounds are present in mixtures. Alkylsulfonutes. A mixture of alkylsulfonates of the general formula NaSOsC,H2,+1 (with n = 14,15, 16, and 17 as main components)was investigated. Mixture analysis was achieved

+

+

1462


Table 11. Investigated Anionic Surfactants and Their Characteristic CAD Fragments m/z

Marlon A 3 5 0 Hostapur [Na,SO,CH( CH,)R]+ C,2H25

precursor (Cat+) [Na,S03]+. [Cat - R]+. [Cat-CH(CH,)R]+.

323 126 154 126

C13H27

337 126 154 126

Figure 4. FD/CAD spectrum of NaSO&H33.

C14H29

351 126 154 126

[NaHS0,C6H,CH(CH,)R]+

[Na,SO,C,H,CH( CH,)R]+

C15H31

C6H13

365 126 154 126

The precursor 1s the [M

315 126 230 202

357 126 230 202

C10H21

371 126 230 202

C11H23

385 126 230 202

C9H19

335

C10H2,

349

+ Na]+ ion.

Figure 5. FD/CAD spectrum of NaS03C6H4C11H23. The precursor is the [U

as described for cationic surfactants using the quasi-molecular ions [Na2S03CnH2n+l]+. Figure 4 shows the CAD spectrum of [Na2S03C16H& (mlz 351) as an example. The spectrum is dominated by the fragment at m / z 126, [Na2S03]+,formed by loss of the alkyl substituent. This fragment allows the rapid determination of the alkyl chain length. Between the ion at mlz 126 and the precursor ion, a series of fragments of the general formula [Na2S03CnHzn]+ with n = 1-15 is observed which facilitates the determination of the chain length further. According to the manufacturer the sulfonate has a branched alkyl chain, Le., NaS03CHR1R2. In all alkylsulfonates the fragment a t m / z 154 is the second most abundant ion in the upper mass range, which most likely is formed by loss of R2 so that R1 must be a methyl group (see Chart I). The branching of the alkyl chain at the carbon in a-position to the

C9H19

343 126 230 202

+ Na]+ ion.

sulfonate moiety also explains why the fragment at mlz 140 (or 139) is particularly weak. The lower mass range is dominated by the sodium ion (mlz 23). Apart from a series of hydrocarbon ions, there is a fragment at mlz 62 of medium abundance, which is most likely [NazO]+. This ion is only observed if the precursor is formed by sodium attachment, but not present in the CAD spectrum of the protonated molecule which supports the structure assignment. In contrast mlz 63 is observed with all anionic surfactants independent of whether the [M + Na]+ or the [M + H]+ is the precursor. As this cannot be a hydrocarbon ion the only reasonable composition is [CH3SO]+. Thus the CAD spectrum allows a rapid identification of the cation, the sulfonate group and the length and branching of the alkyl group.


1463

No 23 [NoHSOjC&CnH2d'

39 Ll

87

I

Flgure 8. FD/CAD spectrum of NaS03CBH4C.,,H23, The precursor is the [M

Chart I. Main Fragmentation Routes of Cationized Alkylsulfonrites

r I Nais037H

1

~3

Cn-2 H2n-3

-1

1

+

Na+(m/z 23) [Na,SOJ (m/z 126) [Na,SO,CHCH,]+ (mlz 154) [Na,O]+ ( m l z 62)

The other componeiits of the mixture show the same fragmentation behavior (see Table 11). The complete spectra are available upon request. Alkylbenzenesulfonates. A mixture of alkylbenzenesulfonates of the general formula N B S O ~ C ~ H ~ C , Hwas ~,+~ investigated where n = 8, 10, 11, 12, and 13 were the main componentsof the mixture. Figure 5 shows the CAD spectrum of [Na2S03C6H4C11H23]+ ( m / z 357) as an example; m / z 126, [Na2S03]+,is again one of the most abundant fragments. The upper mass range is dominated by an abundant fragment at m / z 230. This ion corresponds to m / z 154 observed with alkylsulfonates a n d has t h e s t r u c t u r e [Na2SO3C6H4CHCH3]+..It is formed by benzylic cleavage of the alkyl chain at the branching position. This fragment reveals that the alkyl clhain is branched in exactly the same way as that of the alkylmulfonate. Between the precursor ion and the fragment at mlz 230 a series of ions is observed of the formula [Na2S03CeH4C,H2,]+.whiclh further facilitates the determination of the alkyl chain. Loss of the complete alkyl substituent leads it0 the ion [Na2S(313C6H4]+. ( m / z 202)) which, as expected, is of lower abundance than the product due to benzylic cleavage. In the medium mass range also the fragment at m / z 91 ([C,H,]+) is indicative of the presence of an aromatic substituent. Thus the ions at m / z 91,126,202, and 230 allow an unequivocal and straightforward determination of the structure of the surfactant including the information on the branching position of the alkyl chain. In the lower mass rainge again the sodium ion dominates. Apart from the hydrocarbon ions and thle fragments at m / z 62 and 63, observed alEio with the alkylsulfonates, there are peaks at m / z 46, 87, and 110 which are assigned as Na2+, [NaS02]+,and [Na2SOIl]+.The fact that m/z 46 and 110 are observed only in the CAD spectra of the cationized molecules but not in the spectra of protonated molecules supports these assignments. (The maiin fragments are Summarized in Table 11.) So far only the CAD spectra of the cationized molecules, [M + Na]+,have been discussed. Although these CAD spectra allow an unambiguous Eitructure assignment, a comparison of the CAD spectra of the IM + Na]+ and [M + H]+ is of interest

+ HI+ ion.

from a fundamental point of view. Figure 6 shows the CAD spectrum of [NaHS03C6H4C11H23]+ which can be directly compared with the corresponding CAD spectrum of the cationized ion, shown in Figure 5. As expected the abundant ions at m/z 126, [Na2S03]+,and m / z 62, [Na20]+,are absent which supports the assignments made above. Instead, cleavage of the various C-C bonds in the alkyl chain dominates, leading to a series of ions with the general formula [NaHS03C6H4C,H,]+-. The lower mass range shows the expected abundant sodium peaks and a large number of weaker fragments which are not structure specific and could only be assigned partly. They are not discussed further. Characteristic fragments of all anionic surfactants are summarized in Table 11. Interestingly, in the absence of collision gas still relatively abundant fragments of the type [NaHS03C6H4C,H2n]+.are observed which appear to be formed by unimolecular (metastable) decomposition as shown in Figure 7b for the upper mass range. Such decompositions in the absence of a collision gas are not observed if the cationized ion is studied (Figure 7a) demonstrating the higher stability of [M Na]+ as compared to [M H]+ ions. Nonionic Surfactants. Nonionic surfactants comprise the second most important class of surfactants ( I ) and are usually added to cationic or anionic surfactants to modify the product properties. They usually have a poly(ethy1ene oxide) chain as hydrophilic moiety. Nonionic surfactants are sufficiently volatile to be analyzed by E1 mass spectrometry (7) as discussed in the introduction, although with this technique the molecular ions are of very low abundance (often less than 1% of the base peak) and no preseparation of the individual components is possible. We have investigated two types of nonionic surfactants, i.e., ethoxylated fatty amines and ethoxylated alkylphenols. The FD spectra are dominated by the quasi-molecular ions while fragments are of low abundance. Thus the number of components and their molecular weights can be recognized immediately. Ethozylated Fatty Amines. (See Table 111.) A mixture of ethoxylated fatty amines of the general type Cl2HZ5N[(CH2CH20),H][(CH2CH20),H] where n + m = 2-4, was studied. The FD/CAD spectrum of [Cl2HZ5N(CH2CH20CH2CH20H)2H]+, m/z 363, is shown in Figure 8. The observed fragments correspond with those found under E1 conditions. The main types of ions are summarized in Table 111. Typically, series of fragment ions are observed which are spaced by 44 mass units (C2H,0) and thus reflect the poly(ethy1eneoxide) chains and the number of ethylene

+

+

1464


a

c~2s03c6"c"~231*

b

[N~HSO,C~H, C.HJ 335

3 57

22

x 21 Flgure 7. Metastable ion spectrum of (a) [Na2SO3C8H4Cl1Hz3I+ and (b) [NaHSO3C6H4Cl1Hz3]+ (upper mass range). Ct2%i

[C2H,OHI4 15

k

(C2H60C2HIOH12

11 /I

Figure 8. FDICAD spectrum of Cl,Hz,N(C2H,0CzH40H)2. The precursor Is the [M

+ HI+ ion.

Table 111. Typical Fragment Ions Observed in the CAD Spectra of Nonionic Surfactants structure

type of fragment ion ( m / z ) Ethoxylated Fatty Amines a-cleavage (45) a-cleavage of the alkyl chain (74, 118, 162, 206)

CH,=N+:

or-cleavageof the poly(ethy1ene oxide) chain (198, 242, 286)

C12H25N':

'( CH,CH,O),H

,CH,CH,+ HNI

m = 0, 1, 2 (CH,CH,O),H+ n = 1, 2, 3, 4 [CflH2~C6H40Hl'

n = 1-8 [CnHzn-J+,[CnH,n-i I+, [CnHzn+il+ n = 3,4 C4H3+,C5H,+,C,H,+, CP,'

cleavage of the ether bond and loss of the alkyl chain as olefin (88, 132, 176) (331) hydrocarbon ions (39, 41, 43, 53, 55, 57, , . .) imrnonium ions (44, 58, 72, 86, 100, . . .) Ethoxylated Nonylphenols cleavage of the unbranched alkyl chain (355, 369, 383, 397,411) cleavage of the ether bond + cleavage of the unbranched alkyl chain ( m = 0: 161, 175,189, 203); (m = 1: 205, 219, 233, 247, 261); ( m = 2: 249, 263, 277, 291) ether cleavage (45, 89, 133, 177) rearrangement + cleavage of the alkyl chain (107, 121, 135, 149, 163,177, 191, 205, 219) aliphatic hydrocarbon ions (39, 41, 43, 53, 55, 57) aromatic hydrocarbon ions (51, 63, 77, 91)


[c: 2 ~ 3'

L

~

1465

~

L5

L3

L1

Figure 9, FD/CAD spectrum of CsH,sC,H,(OC,H,),OH.

The precursor Is the [M 4- HI+ ion.

oxide residues can be derived from these ion series. In addition series of hydrocarbon ions and nitrogen-containing ions are found which are less characteristic. This fragmentation behavior can be generalized for all ethoxylated fatty amines. Ethoxylated Alkylphtmols. Two mixtures of ethoxylatecl alkylphenols of the general formula CgHlgC6H40. (CH2CH20),H(n = 3-7) have been analyzed. Figure 9 shows the CAD spectrum of [C$H19C6H40(CH2CH[z0)~H21+, m/z 441, as an example. Again the fragmentation resembles in part that reported for E1 conditions. The most abundant ion in the upper mass range in due to loss of B hexane molecule leading to m / z 355, [ (CH3)2CC6H40(CH2rVH20)~H]+, which immediately reveals how the alkyl chain is branched (see Figure 9). Between this dominant fragment and the quasimolecular ion a series of peaks due to the cleavage of any of the C-C bonds in the hexyl chain is observed, i.e., [C,H2,C(CH3)2C6H40(CH2CH20:lSH]+ with n I4. These peaks have not been observed under E1 conditions. Similarly, not only the ion [C3H6C6H40CH==CH2]+ at m / z 161 is observed (as under E1 conditions) but also the homologous series due to C-C cleavage of the hexyl chain is seen ( m / z 175,189, 203). Moreover, corresponding ion series shifted by 44 or 88 mass units (one or two ethylene oxide units, respectively) are found (see Table 111). Rearrangement reactions lead to alkylphenol ions (m/z 107,128,135, .,.) Furthermore, hydrocarbon ions reflect the aliphatic and aromatic moiety. Finally, in the lower mass range the abundant fragment at m/z 45, [CH2CH20H]+, and homologous ions, [ (CH2CH20),H]+, characterize the hydrophilic substituent. Although the interpretation of the spectra is less straightforward than in the case of the cationic and anionic surfactants, the CAD spectra of the nonionic surfactants reflect readily the main structural features of this compound class, in particular the ethoxylate and the aliphatic hydrocarbon chain and, if present, the benzene ring. However, for an unequivocal structure elucidation, knowledge of the fragmentation pattern of the various types of nonionic surfactants is necessary. Sensitivity. The high transmission of the second stage of the mass spectrometer in conjunction with the simultaneous ion detection system makes the employed tandem mass spectrometer particularly suited for high sensitivity MS/MS studies. To test the sensitivity -5 pg of the cationic surfactant Hoes 2617, [ (CH3)2N(C81Hl7)2]+C1-,was applied to a freshly prepared FD emitter using the syringe technique. While the two test solutions were prepared independently by successive dilution steps, particulair caution was taken to avoid any nondesired sample transportation. The result is shown in Figure 1. The spectrum was obtained by integrating all ions

.

over a period of 80 s, while raising the emitter heating current from 25 to 45 mA (the best anode temperature being at 38 mA). To obtain this spectrum, we reduced the channel plate voltage so that the amplification factor was only 1/50thof the optimum value. Thus good FD/CAD spectra can be obtained from a g sample while the lowest detection limit should be at least 1 order of magnitude lower. It should, however, be mentioned that quaternary ammonium salts (as ionic compounds in general) are known to give particularly high FD ion yields. The results demonstrate the extremely high sensitivity of the instrument employed. Identification of Surfactants from Complex Matrices. While only "pure" industrially manufactured surfactants were analyzed in this study, identification of these compounds from complex matrices should be possible with a minimum of sample pretreatment. Thus in a preliminary experiment cationic, anionic, and nonionic surfactants were identified in two commercially available detergents using a conventional instrument and no sample pretreatment. Although all three groups of surfactants can be identified without prior separation, the simultaneous analysis of all surfactants is facilitated by the fact that the three types of surfactants desorb from the FD emitter at distinct emitter heating currents (see Experimental Section). ACKNOWLEDGMENT The authors are grateful to J. Kistemaker for his enthusiastic support of this work and to J. Dallinga, H. Dassel, and H. v. d. Brink for assistance in performing the measurements. Furthermore helpful discussions with Tauber and Bucking (Hoechst AG) are gratefully acknowledged. LITERATURE CITED Lleonardo, R. A.; Jamieson, R. A. Anal. Chem. 1981, 53, 174R. Longwell, J.; Manlece, W. D. Analyst (London) 1955,BO, 167. Malat, M. Fresenlus' 2.Anal. Chem. 1979, 297,417. Llnhart, K.; Wrabetz, K. Tenslde Deterg. 1978, 75, 19. Nakae, A.: TsuJl, K.: Yamanaka, M. Anal. Chem. 1981, 53, 1818. Llnhart, K.; Wrabetz, K. Tenside Deterg. 1975, 72, 286. Julia-Dan& E.; Casanovas, A. M. Tenslde Deterg. 1979, 16, 317. Bennlnghoven, A., Ed. "Ion Formation from Organic Solids", Sprlnger Serles In Chemical Physlcs, in press. Levsen, K.; Beckey, H. D. Org. Mass Spectrom. 1974,9 , 570. Kondrat, R. W.; Cooks, R. G. Anal. Chem. 1978, 50, 81 A. McLafferty. F. W. Acc. Chem. Res. 1980, 73, 33. Schulten, H A . Int. J. Mess Spectrom. Ion Phys. 1979, 32,97. Levsen, K.; Schwarz, H. Angew. Chem., Int. Ed. fngl. 1976, 75,

509. McLafferty, F. W. A . C . S . Symp. Ser. 1978, No. 70,Chapter 3. Weber, R.; Visel, F.; Levsen, K. Anal. Chem. 1980, 52, 2299. Weber, R.; Levsen, K. Biomed. Mass Spectrom. 1980, 7 , 314. Louter. G.J.; Boerboom, A. J. H., Stalmeier, P. F. M., Tuithof, H. H.; Klstemaker, J. Int. J. Mass Spectrom. Ion Phys. 1980, 33, 335. Louter, G.J.; Buijserd, A. N., submitted for publicatlon in Int. J . Mass Spectrom . Ion Phys

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(19) Beckey, H. D. "Prlnclples of Field Ionization and Field Desorption Mass Spectrometry"; Pergamon: Oxford, 1977. (20) Brent, D. A.; Rouse, D. J.; Sammons, M. C.; Bursey, M. M. Tetrahedron Lett. 1973, 4127. (21) Schulten, H.-R.; Rollgen, F. W. Org. Mass Spectrom. 1975, 70, 649. (22) Schulten, H A . ; Rollgen, F. W. Angew. Chem., Int. M .Engl.. 1975, 74, 561. (23) Veith, H. J. Org. Mass Spectrom. 1978, 11, 629. (24) Sanders, R. A.; De Stefano, A. J.; Keough. T. Org. Mass Spectrom. 1980, 15, 348. (25) Glerllch, H. H.; Rollgen, F. W.; Borchers, F.; Levsen, K. Org. Mass Spectrom. 1977, 12, 387. (26) Velth. H. J. Org. Mass Spectrom. 1978, 73,280. (27) VeRh, H. J. Adv. Mass Spectrom. 1980, 8, 766.

(28) Flscher, M.; Velth, H. J. Helv. Chim. Acta 1978, 67, 3038. (29) Large, R.; Knof, H. J . Chem. Soc., Chem. Commun. 1974, 935. (30) Schulten, H A . ; Kiimmler, D. Z . Anal. Chem. 1978, 278, 13.

RECEIVED for review December 29,1981. Accepted March 3, 1982. This investigation was supported by the "Wissenschaftsministerium Dusseldorf", the "Fonds der Chemischen Industrie, Frankfurt", the Foundation for Fundamental Research on Matter (FOM), and the Netherlands Organization for the Advancement of Pure Research (ZWO).

Structural Elucidation of Drug Metabolites by Triple-Quadrupole Mass Spectrometry Robert J. Perchalskl Research Service, Veterans Admlnistratlon Medical Center, and College of Pharmacy, University of Florida, Galnesville, Florida 32602

Richard A. Yost* Department of Chemistty, University of Florida, Gainesville, Florida 326 1 1

B. J. Wilder Neurology Service, Veterans Administration Medical Center, and College of Medicine, University of Florida, Galnesville, Florida 32602

A tandem quadrupole mass spectrometer wlth a center quadrupole colllslon chamber Is used to determine structures of drug metabolltes by analysts of one plasma or urlne extract. After a chemical Ionization spectrum of the pure drug Is obtalned, a daughter Ion experlment Is run, passing the molecular Ion and characterlstlc fragment Ions through quad 1. Since metabolltes generally contaln a large portlon of the parent drug In their structure, one or more of the daughter ions of the pure drug should be present In each metabollte spectrum. An extract of plasma or hydrolyzed urlne Is then run elther In the parent Ion mode or In the neutral loss mode to obtain, respectively, a spectrum of all parent Ions that fragment to produce the daughter Ions characteristic of the pure drug or a spectruni of parent Ions that fragment by loss of the selected mass difference. Finally, the extract Is run In the daughter Ion mode, to obtain complete daughter spectra of each parent. By appllcatlon of a knowledge of typlcal metabolic pathways, most, If not all, of the metabolltes of a drug can be found In minutes or hours. The valldlty and utlllty of thls method are shown for prlmldone, chromide, and phenytoln.

The marriage of chromatographic methods, particularly gas-liquid chromatography, with mass spectrometry has long been used to successfully determine structures of drug metabolites. Numerous examples of the techniques employed can be found in the continuing series of Gudzinowicz and Gudzinowicz ( I ) and the volume edited by Frigerio and Ghisalberti (2). Methods generally involve some pretreatment of the sample to free conjugated or protein-bound species, followed by liquid-liquid or liquid-solid extraction to separate basic, acidic, and neutral components and endogenous in0003-2700/82/0354-1466$01.25/0

terferences. Since many metabolites are polar molecules, derivatization may be employed to increase volatility, thermal stability, and chromatographic compatibility. This final item is important because compounds that have dissimilar functional groups may not all be detectable under a single set of chromatographic conditions. Therefore,in a metabolite search in which the compounds sought are unknown, use of only one set of conditions may preclude the discovery of one or more species, and developing multiple chromatographic systems takes considerable time. The advent of mixture analysis by tandem mass spectrometry (MS/MS) pioneered in the laboratories of Cooks ( 3 , 4 ) and of McLafferty (5) with the reversed-geometry, doublefocusing mass spectrometer has obviated the need for introduction of a pure sample into the mass spectrometer (chromatographically or on solids probe) and has made possible the analysis of mass-separated ions by a second, on-line technique. In the instrument developed by Cooks and coworkers, the second stage is a kinetic energy analyzer (electric sector) giving rise to the pseudonym MIKES or mass-analyzed ion kinetic energy spectrometry. MS/MS has now been made relatively easy and practica1 by the triple-quadrupole mass spectrometer, introduced by Yost and Enke (6). This instrument consists of an ion source, three quadrupole mass filters, and an ion detector, all in series. The first and third quadrupoles can be set to scan a range of masses or to select one or more molecular or fragment ions. The second quadrupole is enclosed in a cylinder and allows all masses to pass. A collision gas can be introduced into quad 2 to cause fragmentation of ions passed through quad 1 by collisionally activated decomposition (CAD). The daughter ions are then mass analyzed in quad 3. The primary modes of operation are listed in Table I. The quadrupoles can be scanned rapidly, and the various operational modes can be selected by computer at will. These 0 1982 American Chemlcal Soclety

Direct mixture analysis of surfactants by combined field desorption

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