Application
News
Pharmaceuticals / HS-20 GC-2030
Analysis of Residual Solvents in Pharmaceutical
Products by Headspace-GC-FID with Nitrogen Carrier
Gas Following USP<467> - Procedure B
No. AD-0228
❑ Introduction
USP <467> monograph describes Procedure A and B
for analysing residual solvents in pharmaceutical
products by Headspace Gas Chromatography (HS-
GC) [1]. Procedure A is the main method, while
Procedure B is to be carried out as verification when
certain criteria is not met in Procedure A result. In
Application News AD-0209, analysis of residual
solvents in pharmaceutical products was done
following Procedure A which was performed using
nitrogen carrier gas, an inexpensive and abundant
alternative to helium [2]. Here, we describe HS-GC
method using nitrogen as the carrier gas to analyse
Class 1 and Class 2 solvents following USP<467>
Procedure B criteria.
Table 1: HS-GC analytical conditions for residual solvent
analysis following USP <467>
Class 1 Standard
Class 1 Standard (five solvents) was analysed for 7
times to determine the peak area percentage relative
standard deviation (%RSD) and signal to noise ratio
(S/N). The S/N ratios were calculated using USP
method (Table 2). The chromatogram of Class 1
Standard is displayed in Figure 1. Carbon tetrachloride
was co-eluted with 1,1,1-Trichloroethane when
Procedure B was used (Figure 1).
The lowest S/N value for benzene (Peak 4) obtained
was 93, which is greater than the requirement stated in
USP<467> (i.e., S/N ratio is not less than 5). The S/N
ratio for the rest of the Class 1 Standards were greater
than 3 which conformed to the requirement stated in
USP<467>.
The repeatability of peak areas, %RSD (n=7), for the
five solvents (2 solvents co-elute) obtained ranges
❑ Results and Discussion
Instruments and Column information
GC-FID Nexis GC-2030
Auto Injector HS-20
Column
SH-Stabilwax
TM
30 m x 0.32 mm ID x 0.25 μm df
HS parameter
Oven Temperature 80
o
C
Sample Line Temperature 110
o
C
Transfer Line Temperature 120
o
C
Injection Time 1 min
Pressurizing Gas Pressure 75 kPa
Equilibrating Time 60 min
Shaking Level 2
GC-FID parameter
Injection Mode
Split mode
Split ratio 10
Carrier Gas Nitrogen
Gas Flow Condition
Constant linear velocity mode
Linear velocity 35 cm/s
Oven Temperature
Programming
50
o
C (20 min)
→6
o
C/min to 165
o
C (20 min)
Detector Temperature 250
o
C
Hydrogen Flow 32 mL/min
Synthetic Air Flow 200 mL/min
Make-up Gas Flow 24 mL/min
❑ Experimental
Analytical conditions and sample preparation
HS-20 headspace autosampler and Nexis
TM
GC-2030 (Shimadzu Corporation, Japan) were used in
this work. The analytical conditions following
Procedure B under water-soluble article section in
USP<467> are shown in Table 1. Certified USP<467>
Class 1 and 2 Standard solutions were purchased
from Restek. The standards were prepared according
to USP<467> Procedure B before analysis.
Figure 1: HS-GC-FID chromatogram of Class 1 Standard
following Procedure B in USP<467>. Peak labelling refers to
Table 2.
2.0 2.5 3.0 3.5 4.0 min
uV
1
2 & 3
4
5
from 1.8% to 5.1%. These results indicate that when
using nitrogen carrier gas as a substitute of helium
carrier gas, Procedure B criteria can still be fulfilled for
Class 1 Standard.
