JPH01250061A - Gc analysis of compound containing heterocycloamine as molecular structure - Google Patents

Abstract

PURPOSE:To analyze cyclic amines with a simple pretreatment and with good sensitivity by detecting the components separated by a molten silica capillary column with a surface ionization detector. CONSTITUTION:A liquid sample is attached to a tip part 8 of a moving needle 7 which moves upward and downward and thereafter, the tip part 8 is rapidly heated to evaporate the sample in a Van den Bergh type solventless sample introducing device 6. The sample evaporated by the flow of the carrier gas introduced from a carrier gas introducing port 9 is partly introduced into the molten silica capillary column 1 and the rest is discharged from a split-out flow passage 10 to the outside of the system. The cyclic amines separated by the column 1 are converted to positive ions on the surface of a platinum coil 4 heated to 450-600 deg.C of the surface ionization detector 2. The current flowing between a base (not shown) and a collector cylinder 5 is measured by these ions, by which the cyclic amines are detected.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for analyzing compounds containing heterocycloamine as a molecular structure (hereinafter referred to as cyclic amines) by gas chromatography (hereinafter referred to as GC).

(Prior art) Cyclic amines are no longer used as analgesics, skeletal muscle relaxants, tranquilizers, anticancer agents, etc., and many of them have medicinal effects at low concentrations.TDM (Therapeuticall)
With the development of urg monitoring), practical analysis methods are desired.

Conventionally, the analysis of cyclic amines in blood is performed by making the serum alkaline, extracting the drug into an organic solvent, then back-extracting it into an acidic aqueous solution, and then using a packed column to perform 1 1 OC fraction using an electron capture detector (ECD). The flame ionization detector (FIDJ, etc.) was used to perform @ output.

However, the pretreatment operation of performing back extraction after organic solvent extraction is complicated, and there is a large amount of experimental error. Also, since iCI') and F'ID respond to substances other than cyclic amines, they have poor selectivity.

Furthermore, there was a problem in that the sensitivity was insufficient for measuring low concentrations of cyclic amines contained in blood (1 to 5,000 g or less of cyclic amines per 1 m of serum).

(Purpose) The present invention was made in view of the above problems, and its purpose is to provide a selective and highly sensitive analysis method for cyclic amines, and to reduce the time required for analysis. The aim is to propose a 00 analysis method that can be shortened and simplified.

(Summary of the Invention) In other words, the present invention is characterized in that, in the GC analysis method of cyclic amines, a fused silica cavillary column is used as a column, and a surface ionization detector sound is used as a suspension device. do.

In the present invention, cyclic amines is a general term for all compounds that have a cyclic structure containing a nitrogen atom in the molecule and do not have a double bond in the cyclic structure.1 Representative cyclic structures include piperidine rings and cyclic amines. can give pyrrolidine.

Specific drugs include haloperidol, which is an analgesic with a piperidine ring.

Nurpyride and sultoderide, which are tranquilizers, can be used as drugs with a pyrrolidine ring. A GC detector is used that measures the ionization current t of the decomposed gas by bringing it into contact with the gas (Japanese Patent Application No. 106243/1982).

The surface ionization detector is a detector that responds to ammonia and amines, and has a high S degree selectively to cyclic tertiary amines such as nitrogen atoms in piperidine rings and pyrrolidine rings. Amounts of less than a gram can be detected entirely.

In the present invention, a capillary column refers to a column having an inner diameter of 0.6 mm or less.

In the present invention, since the column is a fused silica capillary column, F-cyclic amines can be separated from other impurities with the high resolution of the capillary column, and the total melting strength of the material of the column is As a result, cyclic amines do not undergo tea-linking during separation.

(Children's Embodiment) The details of the present invention will be explained below based on the illustrated baby example.

FIG. 1 shows an example of an OC apparatus used in the present invention. Reference numeral 1 in FIG. 1 is a fused silica cavillary column. 2 is a surface ionization detector, and includes a sudden gaff inlet 3.
Platinum carp/1/4.2-layer collector tube 5 etc.: 9. 6
1 is a Vanden Berg-type solventless sample introduction device, in which the entire liquid sample is introduced into the tip 8 of a moving needle 7 that moves up and down in the figure, and the sample is completely dried by gentle heating.

Part 1-! Alternatively, after repeatedly drying the liquid sample, the tip 8 is rapidly heated to completely vaporize the sample, and the gear gas inlet 9 is introduced into the gear gas inlet 9.
A part of the vaporized sample is introduced into the fused silica cavillary column 1, and the rest is discharged out of the sterit out channel 10 and 9. The cyclic amines separated in the fused silica gear Birarikasim 1 were detected using a surface ionization detector at 20450°C ~ (i
Q Q It is converted to positive ions on the surface of platinum carp/L/4 heated to Ru.

Next, as a simple example of the method of the present invention, vethidium hydrochloride 7 (Ethyl l-metbyl-4-ph) in human serum
enyl-4-piperidineearboxy
An example of analysis of late bydrocblorid+J will be described. 'j-Iv serum 200μeVC vetidine hydrochloride 1. ag/mI! A test solution was prepared by adding 2pe (equivalent to Qng) of an aqueous solution. Add 100 pl of 0.5N sodium hydroxide aqueous solution H and 200 μl of chloroform to the entire amount of this serum.
e was added and shaken vigorously for 1 minute.

After this, 1200 ml was added to separate the aqueous and chloroform layers.
A centrifugation operation was performed at 0 rpm for 10 minutes, and then the entire lower chloroform layer was separated.

This chloroform solution was applied to the tip 8 of the moving needle 7 of the gas chromatograph shown in FIG. 1, dried, and then subjected to GC analysis.

The analysis conditions were a fused silica capillary column CFIPI-850-050 (methyl silicon 0v-1) as column 1.
Equivalent to an inner diameter of 0.33 mm. Length 50m, film thickness 0.5μm,
Column temperature 1zso℃, flow 4m 3.5me/m
, @ As the output device 2, a surface ionization detector, (Shimadzu Corporation S
ID J Sensitivity 2 Purge gas flow rate 4
0 ml, / deception. FIG. 2 is a chromatogram during this analysis of vetidine hydrochloride. As shown by A in the figure, at a retention time of 2.948 minutes, the absolute amount of vetidine hydrochloride was 20 pg.
was detected separately.

(Effects) As detailed above, according to the present invention, cyclic amines can be analyzed with simple pretreatment and with high sensitivity.

[Brief explanation of the drawing]

FIG. 1 is an explanatory diagram showing an example of a GC apparatus used in the present invention, and FIG. 2 is a chromatogram showing a complete analysis of serum containing vetidine hydrochloride according to the present invention. 1...Fused silica capillary column 2...Surface ionization detector 6...Van den Rerg type sop ventless sample introduction device Patent applicant: Shimadzu Corporation. 1.,・τ

Claims (1)

[Claims] A gas chromatography analysis method for compounds containing heterocycloamine as a molecular structure, which is characterized in that components separated by a fused silica capillary column are detected by a surface ionization detector.