Page 50 - Pharmaceutical Solution for Pharma Analysis

LAAN-A-GC-E055

Application Gas Chromatograph

News Analysis of Residual Solvents in drug products using

Nexis GC-2030 combined with HS-20 head space
No. G290 sampler - USP <467> Residual Solvents Procedure A -

Residual solvents in pharmaceuticals are defined as „ Instruments and Analytical Conditions
volatile organic compounds used in or generated from
the manufacture of drug substances, pharmaceutical Table 1 GC Method for USP 467 Procedure A
additives, or drug products. They are strictly controlled Model : Nexis GC-2030
according to risk classifications from Class 1 to Class 3, Detector : FID-2030
which are based on the risk to human health. Headspace Sampler : HS-20
Column : SH-Rxi-624 Sil MS (0.32 mm I.D. × 30 m,
Headspace GC methods specified in the USP (U.S. d.f. = 1.8 μm)
Pharmacopeia), General Chapters <467> Residual Column Temperature : 40 °C (20 min) - 10 °C /min - 240 °C
(20 min) Total 60 min
Solvents, are commonly used for analysis of residual Injection Mode : Split 1 : 5
solvents. This Application News presents data obtained Carrier Gas Controller : Constant Linear Velocity (He)
using the Shimadzu HS-20 Headspace Sampler and Linear Velocity : 35 cm/sec
Detector Temperature
: 250 °C
Nexis GC-2030 Gas Chromatograph, from Class 1 and FID H2 Flow Rate : 40 mL/min
Class 2 standard solutions, in accordance with Water- FID Make up Flow Rate : 30 mL/min (He)
Soluble Articles, Procedure A, in USP <467> Residual FID Air Flow Rate : 400 mL/min
: 1 mL
Injection Volume
Solvents.

E. Kobayashi, T. Murata 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

Nexis GC-2030 + HS-20 1

„ Class1 2
Fig.2 shows the Class 1 standard solution chromatogram. 4
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 5
tetrachloride, which had the lowest sensitivity level, the 3
S/N was 20.
Table 3 indicates the S/N ratio of each peaks and the 0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 11.0 min
repeatability of the peak area (n=6).
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