Application
News
No. G290B
Gas Chromatograph
Analysis of Residual Solvents in drug products using
Nexis GC-2030 combined with HS-20 head space
sampler - USP <467> Residual Solvents Procedure A -
LAAN-A-GC-E055B
Residual solvents in pharmaceuticals are defined as
volatile organic compounds used in or generated from
the manufacture of drug substances, pharmaceutical
additives, or drug products. They are strictly controlled
according to risk classifications from Class 1 to Class 3,
which are based on the risk to human health.
Headspace GC methods specified in the USP (U.S.
Pharmacopeia), General Chapters <467> Residual
Solvents, are commonly used for analysis of residual
solvents. This Application News presents data obtained
using the Shimadzu HS-20 Headspace Sampler and
Nexis GC-2030 Gas Chromatograph, from Class 1 and
Class 2 standard solutions, in accordance with Water-
Soluble Articles, Procedure A, in USP <467> Residual
Solvents.
E. Kobayashi, T. Murata
Fig. 1 Nexis GC-2030 + HS-20
Class1
Fig.2 shows the Class 1 standard solution chromatogram.
Procedure A requires that the S/N ratio obtained for
1,1,1-Trichloroethane in this chromatogram be 5 or
higher. As shown, the S/N ratio was 220. Even for carbon
tetrachloride, which had the lowest sensitivity level, the
S/N was 20.
Table 3 indicates the S/N ratio of each peaks and the
repeatability of the peak area (n=6).
Instruments and Analytical Conditions
Table 1 GC Method for USP 467 Procedure A
Model : Nexis GC-2030
Detector : FID-2030
Headspace Sampler : HS-20
Column : SH-I-624Sil MS
(0.32 mm I.D. × 30 m, d.f. = 1.8 μm)
*1
Column Temperature : 40 °C (20 min) - 10 °C /min - 240 °C
(20 min) Total 60 min
Injection Mode : Split 1 : 5
Carrier Gas Controller : Constant Linear Velocity (He)
Linear Velocity : 35 cm/sec
Detector Temperature : 250 °C
Injection Volume : 1 mL
*1 P/N: 227-36077-01
Table 2 HS-20 Method for USP 467 Procedure A
Oven Temperature : 80 °C
Sample Line Temperature : 110 °C
Transfer Line Temperature : 120 °C
Vial Stirring : Off
Vial Volume : 20 mL
Vial Heat-retention Time : 60 min
Vial Pressurization Time : 1 min
Vial Pressure : 75 kPa
Loading Time : 1 min
Needle Flush Time : 5 min
Fig. 2 Chromatogram of WATER-SOLUBLE ARTICLES Class1
Standard Solution by Procedure A
Table 3 S/N ratio and Repeatability of Class1
No. Compounds S/N ratio %RSD (n=6)
1 1,1-Dichloroethane 320 2.8
2 1,1,1-Trichloroethane 220 2.3
3 Carbon tetrachloride 20 2.9
4 Benzene 170 2.5
5 1,2-Dichloroethane 60 3.4
0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 11.0 min
1
2
4
5
3
