Page 58 - Pharmaceutical Solution for Pharma Analysis

C146-E338

Using GCMS to Test

for Residual Solvents in Pharmaceuticals

1 Introduction

The HS-GC-FID method is used to test for residual solvents in pharmaceuticals, but GC-MS is useful for identifying peaks in close
proximity or for qualifying unknown peaks. However, to qualify peaks detected by GC-FID using GC-MS requires matching
chromatogram patterns. The advanced flow controller (AFC) in GC-2010 Plus systems includes constant linear velocity control as
standard functionality. This allows achieving similar retention time and separation patterns in GC-FID and GC-MS chromatograms by
specifying the same linear velocity setting, provided the columns are identical or columns with the same phase ratio are used.

2 Analytical Conditions to Test for Residual Solvents in Pharmaceuticals
Testing for residual solvents in pharmaceuticals involves using a separation column with a 0.53 mm (or 0.32 mm) internal diameter,
30 m length, and 3.0 µm (or 1.8 µm) thick cyanopropyl phenyl-based liquid phase and separation conditions with a linear carrier gas
speed of 35 cm/sec (Procedure A). However, those separation conditions cannot be achieved using GC-MS, due to the negative
pressure (vacuum) at the column outlet. Therefore, the typical method used to obtain similar chromatogram patterns is to downsize
the column to one with a small internal diameter, so that the phase ratio (ratio of column internal diameter to film thickness) is the
same.

SH Rxi-624sil MS SH Rxi-624sil MS
0.32 mm I.D., 30 m long, and 1.8 µm 0.25 mm I.D., 30 m long, and 1.4 µm
film thickness film thickness

This results in similar chromatogram patterns
using the same linear velocity of 35 cm/sec.

Control by the AFC takes into consideration the difference in column outlet pressure between GC and GC-MS. For HS-GCMS analysis,
it simply requires changing the column and specifying a 35 cm/sec linear velocity in the method parameter selection window in
GCMSsolution. During analysis, the AFC controls the carrier gas automatically, which eliminates the inconvenience of having to
adjust pressure or other settings.

GCMS-QP2020 + HS-20 + FID-2010 Plus Detector
By including an FID detector in the HS-GCMS system, either
analytical method can be used. Contact a Shimadzu representative
regarding changing the system configuration, which can be
modified to accommodate various user requirements.