Method and apparatus for introducing samples to a mass spectrometer

Simplified method and apparatus for connecting a liquid chromatograph, particularly of a high-performance type, directly to a mass spectrometer without using any complicated devices conventionally available, for the purpose of continuous and stable mass spectrometric measurement of a liquid sample, either liquid or solution, more commonly an effluent supplied directly from a column of the liquid chromatograph or an aliquot portion thereof extracted through a simple and ordinary splitter, or any other liquid samples prepared for the mass spectrometric analysis. Such a liquid sample is first sprayed into finely divided particles by a nebulizing means mainly consisting of a double-tubing capillary so that the sample is easily vaporized, and finally introduced into an ionizing portion of the mass spectrometer in continuous and stable manner.

BACKGROUND OF THE INVENTION 
The present invention relates generally to introduction of a sample to a 
mass spectrometer (MS) and is more particularly concerned with simplified 
method and apparatus by which a liquid sample is nebulized into fine 
particles in extremely efficient manner to facilitate vaporization thereof 
and the nebulized liquid sample is then continuously introduced to the MS 
thereby enabling the MS to handle a wider range of compounds for mass 
spectrometric measurement. 
A mass spectrometer (MS) has been widely used as an instrument for 
performing both qualitative and quantitative analyses of different gases, 
volatile liquids and solid molecules by obtaining mass spectra thereof 
through measuring an ion current caused by ions collected on one or a 
plurality of fixed ion collector electrodes while adjusting or varying the 
accelerating potential and intensity of the magnetic field. In recent 
years, it has been attempted to employ such an MS in connection with 
another type of separating and analyzing instruments for efficient 
analysis of mixtures. 
For example, a liquid chromatograph (LC), especially a high-performance 
liquid chromatograph (HLC), has attracted a good deal of attention in this 
field and is presently accepted as an excellent means for separating a 
mixture into its constituents and determining the individual constituents 
quantitatively or volumetrically mainly because it is capable of 
separating either fat- or water-soluble substances into its components, 
without any preliminary modification of such substances, by simply making 
a proper choice of a solvent and a separation column. Although such an HLC 
is given a surpassing capability of separating mixtures per minute, it has 
a disadvantage that it is not completely satisfactory in its ability of 
identifying the separated constituents. The mass spectrometer (MS), on the 
other hand, is extremely high in its sensitivity and performance in 
identification of a single component but it has also a disadvantage, at 
the same time, that it is accompanied with considerable difficulty when 
identifying a mixture because the spectra to be obtained are complicated. 
To make the effective use of the advantages and make up the disadvantages 
of both LC and MS instruments, there has been presented a LC-MS analyzing 
system which is a combination of the two. 
Further, the analysis by mass spectrometry with use of the MS encounters 
various sorts of problems when the sample to be handled is a liquid or a 
solution of any solvent because the mass spectrometric analysis is 
achieved by ionizing the sample after it is converted into a gas state. In 
other words, any sample which is a liquid or solution requires 
vaporization thereof before it is introduced to an ionizing portion (ion 
source) of the MS. However, it is an extremely hard practice to attain 
continuous yet stable vaporization of such a liquid sample and the 
subsequent introduction thereof to the ion source especially when the 
sample is a polar or large molecular-weight compound. The compound LC-MS 
analyzing system previously described also has a potential of suffering 
from problems similar to those of the MS above indicated because the 
sample to be introduced to the MS of the system is an effluent from the 
separation column of the LC, which is a liquid. The most contributing 
causes preventing practical use of the LC-MS analyzing method are its 
difficulty in continuously removing a solvent (mobile phase) from a 
continuous flow of the effluent supplied, and the resultant failure in 
offering an effective means for concentrating the desired constituent 
present in the effluent. 
To solve such problems as stated above, a variety of methods and procedures 
for introducing the liquid samples to the MS have been examined and 
proposed up to the present. Some of the most positively attempted 
solutions to the problems have been concerned with development of a 
so-called "interface", i.e. a means for connecting the LC to the MS to 
establish a LC-MS combined analyzing system, on which the spotlight of 
research workers' attention has been focused. Up to date, however, only a 
few reports of research on the LC-MS connecting methods have been made 
public, including the following: 
(1) LC-EIMS Method 
The LC-EIMS Method [J. Chromatogr., 99, 395 (1973)], which was developed by 
R. P. G. Scott et al. is characterized by a fine stainless steel wire 
traveling through an ion source of the MS wherein the ionization is 
carried out by an electron impact (EI). Approximately one percent (1%) of 
the effluent from the MS adheres to a portion of the traveling wire 
outside the housing of the MS and the solvent in the effluent adhering to 
the wire is removed during its travel through a preliminary heating and 
evacuation system whereby only the desired constituent of the effluent is 
finally introduced into the ion source. To ensure higher sealing 
performance of individual interface chambers which are in communication 
with the preliminary heating and evacuation system, the wire is passed 
through small jewel apertures provided in each of partition walls 
separating from one chamber to another. Scott et al. state in their report 
that this method is applied to handling mixtures of several different 
drugs and metabolites and of fermented products, and that the desired 
constituent detected and identified by the method ranges from 10.sup.-6 to 
10.sup.-7 g per ml of the mixture to be handled. However, the method 
retain not a few points that should be improved before it is put into 
practice, including its possibility that the sample being fed by the wire 
may stick to the jewel apertures or the sample sticking to the apertures 
may be mixed with the newly fed sample on the wire while the wire is 
traveling through the apertures, as well as its insufficient capability of 
quantitative analysis. 
(2) Direct Chemical Ionization (DCI) Method 
The direct chemical ionization method [Org. Mass Spectrom., 7, 1353(1973)] 
was developed by McLafferty et al. It is well known that the chemical 
ionization (CI) method is effective in a combined system of a GC (gas 
chromatograph) and an MS. In a system of an LC coupled with the MS, 
however, there is a considerable difficulty in removing entirely the 
mobile phase of the LC which is a liquid. To overcome this difficulty of 
the LC-MS system, is proposed this DCI method which is intended to 
introduce a desired constituent of the effluent from the LC column 
together with the solvent thereof without previous removal of the latter, 
and to utilize the solvent vapor as a reagent gas thereby measuring the CI 
spectra. In the DCI method, an elution speed of the LC and a way of 
introducing the effluent to the ion source of the MS hold important keys 
to successful measurement of the CI spectra. But as far as these two 
conditions are properly established, the CIMS (Chemical Ionization Mass 
Spectrometer) is more easily connected to the LC than the EIMS (Electron 
Impact Ionization Mass Spectrometer), and has a potential of continuous 
measurement of the CI spectra. McLafferty et al. designed the LC-CIMS 
interface so that approximately one percent (1%) of the effluent from the 
LC is conducted through a glass capillary tube (0.076 mm in diameter) into 
the ion source. They applied the interface to a mixture of different 
steroids each being of 0.8 .mu.mol and obtained a good result. However, 
this interface method has some disadvantages. At first, amount of effluent 
that can be used is as less as 1% and in addition, it is very difficult to 
manufacture the glass capillary which is so small in diameter. Even if it 
was possible, it would be a hard practice to feed the effluent through 
such a fine capillary. Another disadvantage of this method is caused by 
the fact that the effluent is introduced directly into a heated ion 
source. As a result, the introduction of the effluent is easily and 
frequently interrupted due to bumping or other phenomena at the ion 
source. This disadvantage has made it difficult to accomplish a continuous 
and stable vaporization of the effluent. 
As indicated above, any one of the conventionally-available interfaces 
between the LC and MS instruments has a number of inherent problems such 
as complicated construction, less ease of operation and extremely high 
manufacturing cost, and in general, fails to completely satisfy the 
requirements as a practicable device. The conventional failure in 
providing the practicable interface device means that there is not yet 
developed any method and device commonly available for introducing liquid 
samples to the MS. To put the LC-MS analyzing procedure into practice, it 
is an urgent matter and need to provide a proper method for the liquid 
sample introduction to the MS and to develop an apparatus which is simple 
in construction, easy in operation, high in sample concentrating 
capability and performance, and low in manufacturing cost. 
SUMMARY OF THE INVENTION 
Through extensive and intensive research and experiments in view of the 
above need, the inventors have come to the conclusion that all of the 
previously indicated problems and disadvantages may be solved 
satisfactorily by adopting a nebulizing method by which a liquid sample to 
be analyzed is sprayed into finely divided particles before the same is 
introduced into the MS whereby even compounds which have been otherwise 
difficult to be analyzed on any conventional MS may also be handled with 
quite ease. This sample nebulizing method is found considerably effective 
and advantageous. 
Accordingly, it is the principal object of the present invention to provide 
method and apparatus for introducing liquid samples to a mass 
spectrometer. 
It is another object of this invention to provide method and apparatus for 
facilitating the vaporization of most of the polar and/or large 
molecular-weight compounds before the introduction thereof to the ion 
source of the MS, which is otherwise difficult conventionally, thereby 
making it possible to measure the mass spectra and in addition, to permit 
a continuous and stable introduction of the liquid sample to the MS. 
Further object of the invention is to provide an interface for connecting 
an LC, particularly an HLC directly to an MS, thereby allowing an LC-MS 
analizing procedure to be put into practice. 
It is still a further object of the invention to provide a 
simply-constructed, easy-to-operate and highly efficient sample 
introducing apparatus wherein the liquid sample is sprayed into finely 
divided particles by use of a nebulizing method for attaining easy and 
effective vaporization and continuous supply of the sample to the MS and, 
at the same time, making it possible to achieve the concentration of the 
liquid samples which has been considered difficult on any conventional 
apparatus. 
Other objects of this invention will become apparent to those skilled in 
the art from the following detailed description of the preferred 
embodiments when read in connection with the accompanying drawings. 
To attain these objects of this invention, a nebulizing gas is supplied to 
a nebulizing means and spurted forth from a nozzle portion of the 
nebulizing means while a liquid sample is continually fed to the nozzle 
portion whereby the liquid sample is nebulized by a jet stream of the 
nebulizing gas gushed from the nozzle portion and the liquid sample thus 
nebulized is finally introduced to an ion source of a mass spectrometer 
(MS). Another feature of this invention to effect the foregoing objects is 
the provision of a double-tubing capillary mainly acting as a part of the 
nebulizing means and comprising an external tube and an internal tube 
received coaxially within the external tube. The liquid sample is 
conducted through the internal tube while the nebulizing gas is introduced 
through a space formed between an outer surface of the internal tube and 
an inner surface of the external tube whereby the liquid sample is 
nebulized in stable and effective way at the nozzle portion located at one 
end of the double-tubing capillary. 
In accordance with this invention previously characterized, the liquid 
sample fed to and ejected from the nozzle portion at the end of the 
double-tubing capillary described above as nebulized or sprayed into fine 
particles by the jet stream of the nebulizing gas spurted from the nozzle 
portion and thus becomes extremely easy to vaporize. Thus, this invention 
is significantly effective for vaporizing polar and/or large-molecule 
compounds or any organic compounds of which mass spectrometric measurement 
is conventionally difficult, and for achieving efficient mass 
spectrometric detection and identification thereof. The liquid sample 
sprayed into fine particles in such manner as previously stated by the 
nebulizing means is continuously and stably introduced to the ionizing 
portion of the MS because most of the sprayed particles are vaporized in 
advance through the aid of heat applied thereto and/or under a high degree 
of vacuum established in the MS although a portion of the liquid sample 
enters the ionizing portion while remaining in a state of fine particles. 
Another feature of the invention is that the neblization of the liquid 
sample is carried out in an evacuated chamber and the nebulized sample is 
then conducted to another chamber under reduced pressure. Therefore, a 
volatile solvent in the liquid sample is vaporized and the vaporized 
solvent is sucked into an evacuation source (vacuum source) which 
maintains the solvent vapor under the reduced pressure whereby the solvent 
in the fine particles of the nebulized sample is removed resulting in the 
concentration of the solute (the desired constituent of the liquid 
sample). Furthermore, the apparatus in accordance with this invention is 
extremely easy to operate, significantly simple in construction and 
considerably low in manufacturing cost because the objects of the 
invention are attained simply by nebulizing the liquid sample.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
Referring now more particularly to the accompanying drawings which 
illustrate preferred embodiments of this invention, a cross sectional view 
of an apparatus (interface) in accordance with the invention is presented 
in FIG. 1 wherein the apparatus is provided with a nebulizing nozzle 
portion whose enlarged sectional view is given in FIG. 2. In the drawings, 
a double-tubing capillary 1 comprises an external tube 1a of 
heat-resistant or heat-resisting glass and an internal tube 1b also of 
heat-resistant glass being coaxially received within the external tube 1a. 
The internal tube 1b is inserted past a plug 2 fitting in one end of the 
external tube 1a and connected to a conduit 3a which is in communication 
with a column 3 of a liquid chromatograph (LC), whereby an effluent E from 
the column 3 is conducted into the internal tube 1b. A nebulizing gas 
[Helium (He) is used herein.] from the supply source not shown in the 
drawing is introduced into a passage 5 formed between an inner surface of 
the external tube 1a and an outer surface of the internal tube 1b, through 
the conduit 4 penetrating the plug 2. As illustrated in FIG. 2, the 
external tube 1a has progressively decreasing inside and outside diameters 
at the other end thereof opposite to the one in which the plug 2 is 
fitted, and the internal tube 1b extending through this progressively 
decreasing diameter portion projects a slight distance away from said 
other end of the external tube 1a, whereby the nebulization of liquid 
samples is attained with higher efficiency as described later. Thus, the 
end portions of the external and internal tube 1a and 1b constitute a 
nebulizing nozzle portion 1c of the double-tubing capillary 1. Within the 
internal tube 1b including the nozzle portion 1c, there is inserted a 
piano (steel) wire 7 as a core thereof which is given a proper amount of 
clearance from the inner surface of the internal tube 1b to provide a 
passage 6 through which the effluent E is continuously and stably fed to 
and ejected or discharged from the end of the nozzle portion 1c (internal 
tube 1b). The nozzle portion 1c of the double-tubing capillary 1 of this 
preferred embodiment has the specifications which follow: 
The external tube 1a is 0.4 mm in inside diameter, the internal tube 1b 
0.35 mm and 0.15 mm in outside and inside diameters, respectively, and the 
piano wire 7 0.13 mm in diameter. The projecting distance of the internal 
tube 1b from the end of the external tube 1a is approximately 0.3 mm. 
The double-tubing capillary 1 as specified above is inserted into a 
heat-resistant glass tubular body 8 from one end of the same body 8, in 
such way that the nozzle portion 1c thereof is located within a nebulizing 
chamber 9 formed within the interface body 8 with a partition wall 8a, and 
secured to said one of the interface body 8 by a cap nut 11a and a 
threaded retainer plug 11b through an O-ring 10 whereby the nebulizing 
chamber 9 is sealed to an evacuation system. The nebulizing chamber 9 is 
connected to a rotary vacuum pump 12 by which an intended degree of 
reduced pressure (vacuum) is maintained in the chamber 9. A heat-resistant 
glass tube 13 introducing the nubulized sample to the MS is formed 
coaxially and as a integral part of the interface body 8, penetrating the 
partition wall 8a. In the nebulizing chamber 9, one end of the 
introduction tube 13 is opposed to the end of the nozzle portion 1c of the 
double-tubing capillary 1 as an orifice through which the nubulized sample 
from the nozzle portion 1c enters into the introduction tube 13. The 
orifice of this embodiment is of 0.5 mm diameter. The other end of the 
introduction tube 13 is extended into a body 14 of the MS through an end 
portion of the interface body 8 which is secured to the end of the body 14 
by a retainer screw 16a and a nut 16b through O-rings 15a and 15b, and 
connected to an ordinary ionizing chamber 17 provided in the MS, whereby 
the liquid sample (effluent E) nebulized in the nebulizing chamber 9 is 
introduced into the ionizing chamber 17. 
A portion of the interface body 8 including the nebulizing chamber 9 is 
heated to any desired temperature not higher than approx. 300.degree. C. 
in the nebulizing chamber 9 and its vicinity by a heating oven 18 (shown 
in FIG. 1 by dashed lines) disposed round the interface body 8, for the 
purpose of compensating for the latent heat of vaporization of a solvent 
lost during nebulization of the effluent E. In addition, the introduction 
tube 13 is also heated as desired up to approx. 300.degree. C. by a heater 
20 through a heater sheath 19 disposed along the periphery thereof so as 
to permit the nebulized liquid sample to be introduced into the ionizing 
chamber 17 of the MS without being stuck or adsorbed to an inner surface 
of the tube 13 (due to condensation of the nebulized sample or any other 
causes). 
In operation of the apparatus featuring such construction and arrangement 
as mentioned above, the effluent E from the column 3 of the LC is 
conducted through the conduit 3a into the internal tube 1b of the 
double-tubing capillary 1 and continually introduced into the nebulizing 
chamber 9 through the passage 6 formed between the internal tube 1b and 
the piano wire 7. The introduction of the effluent E into the nebulizing 
chamber 9 is accomplished either by evacuating the chamber 9 or by 
force-feeding the effluent E with use of a pump provided outside the 
interface system. On the other hand, the nebulizing gas He supplied 
through the conduit 4 is introduced into the passage 5 formed between the 
external and internal tubes 1a and 1b of the double-tubing capillary 1 and 
is spurted from the nozzle portion 1c of the capillary 1 at a high rate. 
Consequently, the effluent E fed to the end of the nozzle portion 1c is 
continuously sprayed into the nebulizing chamber 9 as finely divided 
particles by a jet stream of the nebulizing gas He. Because the nebulizing 
chamber 9 is maintained under an intended degree of reduced pressure by 
its exposure to a high level of vacuum in the MS as well as by the 
operation of the rotary pump 12 and because it is heated, at the same 
time, to prevent the solvent from dripping from or frosting on the nozzle 
portion 1c due to cooling effect mainly caused by the latent heat of 
vaporizaton, an aliquot portion of the nebulized effluent E (air sol) is 
freed of solvent and becomes dried air sol under vacuum and heat, and the 
entire air sol including the dried portion enters through the orifice into 
the introduction tube 13 and finally is introduced to the ionizing chamber 
17 under higher vacuum in the MS. In this way, at least aliquots of a 
low-boiling solvent contained in the effluent E are vaporized in the 
nebulizing chamber 9 whereby the nebulized effluent E becomes more finely 
divided particles easy to vaporize. Further, the vaporized solvent is 
removed through suction by the rotary pump 12, and therefore the nebulized 
effluent E is easily concentrated (a higher degree of concentration of the 
desired constituent or solute may be easily achieved.). Thus, the 
concentrated particles of the effluent E are finally introduced to the 
ionizing chamber 17 thereby increasing the efficiency of mass 
spectrometric measurement of the effluent E. Although a minor portion of 
the finely divided particles containing the desired constituent (solute) 
to be measured is previously vaporized in the nebulizing chamber 9, a 
major portion thereof enters continually into the introduction tube 13 
through the orifice opposing the nozzle portion 1c after being freed of 
solvent into more vaporous state, whereby the vaporization is efficiently 
effected while traveling through the tube 13 under higher vacuum of the MS 
and with heat applied thereto by the heater 20 and another heating source 
commonly provided in the MS. In accordance with this preferred embodiment 
of the invention as described so far, a liquid sample or effluent from the 
LC may be efficiently introduced to the MS by continuously nebulizing it 
into finely divided particles prior to the final introduction thereof to 
the MS. This means that the apparatus presented in the embodiment makes it 
possible to directly couple the MS to the LC. 
Although it is so designed in this embodiment that the effluent E from the 
column 3 is entirely introduced into the internal tube 1b of the 
double-tubing capillary 1 through the conduit 3a which is directly 
connected to the tube 1b, it is of course possible to provide a proper 
splitter to feed only an aliquot portion of the effluent E into the 
internal tube 1b. However, the primary feature of the interface in 
accordance with this invention is its surpassing capability of directly 
coupling an MS with an LC (particularly HLC) into a combined analyzing 
system, which has not been offered on any conventional interfaces. Another 
feature of the interface of this invention is the ability to handle any 
ordinary solutions or liquids prepared as a sample to be introduced to the 
MS for mass spectrometric analysis, as well as effluents from the LC. In 
handling such prepared solutions or liquids, they are pumped into the 
internal tube 1b. Further feature of this invention is the versatility to 
employ a wide variety of nebulizing gas unless it has a disadvantageous 
effect on the mass spectrometric measurement. Gases usable as a nebulizing 
gas include: helium (He) as used herein, nitrogen, argon, methane, 
isobathane and ammonia. 
While, in the previously described embodiment, the piano wire (not limited 
to the piano wire as far as it is made of a metal) is provided as a core 
wire within the internal tube 1b of the double-tubing capillary 1 to 
reduce dead volume of the tube 1b for continuous and stable introduction 
of the effluent E into the nebulizing chamber 9, a similar effect is 
obtained by using the internal tube 1b of a reduced inside diameter. 
Practicably, however, it is recommended that the internal tube be used 
with a core wire being inserted therein as in the previous embodiment when 
taking into account the ease of retention within the external tube 
(mechanical strength), servicing and maintenance thereof (ease of cleaning 
the nozzle portion 1c even when plugged). From the standpoint of such 
practicability, double-tubing capillary comprising an external tube and an 
internal tube is preferable also as a nebulizing means. Although the piano 
wire 7 is inserted over the entire length of the internal tube 1b, its 
length may be reduced as far as it can cover the nozzle end portion of the 
internal tube 1 b. 
And while the nebulizing chamber 9 of the previous embodiment of this 
invention is connected to the vacuum source 12 and the effluent E is 
nebulized under reduced pressure with significant efficiency, it is also 
possible to nebulize the effluent under atmospheric pressure by making use 
of Atmospheric Ionization (API) method well known as a means for ionizing 
gaseous samples. Further, to attain efficient introduction of the 
nebulized effluent into the MS, it is preferable that the diameter of the 
orifice at the end of the introduction tube 13 opposing the nozzle portion 
1c be larger than the inside diameter of the external tube 1a at the end 
of the nozzle portion 1c and that the distance between the orifice of the 
introduction tube 13 and the end of the nozzle portion 1c be adjusted to 
suit the particular suction pressure of the rotary pump 12, amounts of the 
fine particles produced in the chamber 9 and those introduced into the MS, 
and so forth so that a proper level of pressure (for example, 1 Torr) is 
established in the chamber 9. The vaporized liquid sample (effluent) may 
be ionized in the MS by any one of the publicly known methods. For 
example, in case the amount of introduced solvent vapor is relatively 
large, the Chemical Ionization method using the solvent as a reagent gas 
is suitably applied. When the same amount is comparatively small, on the 
contrary, the ordinary Electron Impact Ionization or Field Ionization 
method is applicable. 
While a preferred embodiment has been described, it is to be understood 
that this invention is not limited to this precise form of method and 
apparatus, and that changes and modifications may occur to those skilled 
in the art without departing from the spirit and scope of the invention. 
As an example, there is illustrated in FIG. 3 an alternative embodiment of 
this invention presenting a modified interface which differs from that 
shown in FIG. 1. mainly in the means for introducing the nebulized 
effluent from the nebulizing chamber to an MS. While the interface shown 
in FIG. 1 may be connected to any conventional MS with substantially no 
modification of the latter, the interface presented in this alternative 
embodiment is specifically adapted to as MS wherein an ionization chamber 
is located adjacent to the wall of the MS body, and thus capable of 
introducing the nebulized liquid sample directly into the ionizing chamber 
of the MS. Any description of parts apparatus of this alternative 
embodiment similar to those of the previous embodiment is omitted herein 
by designating them with the same reference characters. The following 
description refers only to the difference in the parts arrangement and 
construction between the two embodiments. In the apparatus illustrated in 
FIG. 3, a pinhole 22 is provided in a plate-like member 21 attached to an 
outer wall of the MS body, as a means for introducing the nebulized 
effluent into the MS. The pinhole 22 is disposed so that it is opposed to 
the nozzle portion 1c of the double-tubing capillary 1. Through this 
pinhole 22, the liquid sample is sucked directly into the ionizing chamber 
17 under a high degree of vacuum in the MS, and finally ionized therein 
after it is vaporized under such vacuum and heat generated by a heat 
source 17a commonly provided in the ionizing chamber 17. The apparatus of 
this alternative embodiment is recommended mainly because it is generally 
preferable that a length of travel of the nebulized liquid sample to the 
ion source (ionizing chamber) be as short as possible. Unlike the 
apparatus of the previous embodiment, the apparatus of this embodiment is 
not provided with the heating oven 18 to heat the nebulizing chamber 9. 
This is because the heat souce 17a in the ionizing chamber 17 is located 
adjacent to the nozzle portion 1c and is capable of supplying an 
appropriate quantity of heat to make up for the latent heat of 
vaporization during nebulization of the liquid sample in the nebulizing 
chamber 9. Of course, it is possible and necessary to provide a proper 
heating means such as the heating oven 18 and the heater 20 provided in 
the previous embodiment when the quantity of heat supplied from the 
ionizing chamber 17 is not sufficient. 
There is shown in FIG. 4 another alternative embodiment of this invention 
which is characterized by the nebulizing chamber 9 and a following 
concentrating chamber 23 formed as integral parts of the interface body 8, 
and connected in series to each other by a connection tube 24 of 
heat-resistant glass. The concentrating chamber 23 is also connected to a 
rotary pump 25 whereby the concentrating chamber 23 is kept under reduced 
pressure lower than that in the nebulizing chamber 9. The connection tube 
24 is formed with one end thereof being opposed to the nozzle portion 1c 
in the nebulizing chamber 9. The same end has a tapered bore progressively 
increasing in diameter toward the nozzle portion 1c for efficient 
introduction of the nebulized liquid sample from the nozzle portion 1c 
into the concentrating chamber 23. In addition, the introduction tube 13 
is disposed so that one end thereof is opposed to the other end of the 
connection tube 24 located in the concentrating chamber 23. In the 
drawing, reference characters 8b indicate a partition wall similar to 8a, 
and numerals 26 and 27 represent spacers for retaining the internal tube 
1b and the double-tubing capillary 1, respectively. As in the previous 
embodiment shown in FIG. 1, a heating oven 18 is provided round the 
interface body 8 for heating at least the nebulizing chamber 9, 
concentrating chamber 23 and their vicinity. 
In the apparatus of this alternative embodiment having such construction 
and parts arrangement features as described above, the liquid sample is 
first sprayed from the nozzle portion 1c of the double-tubing capillary 1 
into the nebulizing chamber 9 under an intended level of reduced pressure, 
and concentrated therein to a certain extent. The liquid sample thus 
nebulized and partially concentrated is then fed through the connection 
tube 24 into the concentrating chamber 23 of more reduced pressure wherein 
a solvent present in the sample is vaporized and removed (sucked into the 
rotary vacuum pump 25) for more concentration of the desired constituent 
or solute. From the concentrating chamber 23, the sample is conducted into 
the MS through the introduction tube 13. Thus, the liquid sample is 
introduced into the MS with significantly high efficiency. Experiments by 
the inventors revealed that an interface having such concentrating chamber 
was able to connect the MS directly to a large-capacity LC of effluent 
flow rate as high as 200 .mu.l/min. Although this alternative embodiment 
uses only one concentrating chamber, there may be employed two or more 
concentrating chambers provided that they are connected to respective 
vacuum sources and evacuated to progressively reduced pressures from the 
nebulizing chamber to the MS. 
As detailed above, the present invention provides simplified method and 
apparatus for directly connecting a liquid chromatograph (LC), 
particularly a high-performance liquid chromatograph (HLC) to a mass 
spectrometer (MS) without using any complicated devices conventionally 
available, for the purpose of continuous and stable mass spectrometric 
measurement of a liquid sample, either liquid or solution, more commonly 
an effluent directly from a column of the LC (HLC) or a portion thereof 
extracted through a simple and ordinary splitter, or any other liquid 
samples prepared for the mass spectrometric analysis. Such a liquid sample 
is first sprayed into finely divided particles by a nebulizing means 
including a double-tubing capillary to facilitate vaporization of the 
sample, and finally introduced into an ionizing portion of the MS in 
continuous and stable manner. The provisions of such method and apparatus 
in accordance with this invention is extremely significant because of the 
following advantages and features: At first, operation of a combined LC-MS 
analyzing system is made easier than ever before. Secondly, it becomes 
possible to attain concentration of an effluent or any other liquid sample 
which is conventionally considered a difficult practice. Thirdly, it is 
made possible to handle a wide range of samples for mass spectrometric 
detection and identification, including comparatively 
difficult-to-vaporize compounds of low vapor pressure, and polar or 
large-molecule compounds such as aromatic amines, drug components, 
steroids, amino acids, oligopeptides and polyethyleneglycols. In addition, 
the apparatus of this invention is considerably high in performance and 
practicability, comparatively low in manufacturing cost as it is made of a 
glass, and in addition, highly inert to components of a sample (solute and 
solvent).