Page 52 - Pharmaceutical Solution for Pharma Analysis

LAAN-A-MS-E038

Application Gas Chromatography Mass Spectrometry

News Analysis of Residual Solvents in Pharmaceuticals

Using Headspace GC-FID/MS Detector Splitting
No.M272 System

Headspace gas chromatography with flame ionization Table 1 Analytical Conditions
detection (GC-FID) is often used for residual solvent Headspace Sampler :HS-20
testing of pharmaceuticals, though the qualitative GCMS :GCMS-QP2020
power of this method is not particularly high. Because Hydrogen Flame Ionization Detector :FID-2010Plus
gas chromatography mass spectrometry (GC/MS) Splitting System
utilizes MS to perform qualitative analysis based on
mass spectra, GC/MS can be used to estimate and HS
identify individual peaks detected in the expected Mode :Loop (volume 1 mL)
vicinity of a target solvent as well as other unknown Oven Temp. :80 °C
Sample Line Temp.
:90 °C
peaks. Transfer Line Temp. :105 °C
We describe an example of residual solvent test of a Gas Pressure for Vial Pressurization :76.4 kPa
pharmaceutical using a detector splitting system that Vial Equilibrating Time :45 min
simultaneously obtains FID and MS data in a single Vial Pressurizing Time :2.0 min
measurement. Pressure Equilibrating Time :0.1 min
Load Time :0.5 min
Load Equilibrating Time :0.1 min
n Sample Preparation
Injection Time : 0.5 min
According to Water-Soluble Articles, Procedure A, in Needle Flushing Time :15.0 min
USP <467>, we prepared a class 1 standard solution, APC Pressure :20 kPa
class 2 standard solution A, class 2 standard solution B,
test solution, and class 1 system suitability solution. An GC
active pharmaceutical ingredient was used for the test Column :SH Rxi-624sil MS
solution sample. (30 m × 0.32 mm I.D., 1.8 µm)
Injection Mode :Split (split ratio 1:5)
Control Mode :Constant Pressure (89.4 kPa)
n Analytical Conditions Carrier Gas :He
The image of the Shimadzu GCMS-QP2020/FID detector Oven Temp. :40 °C (20 min) → 10 °C/min →
240 °C (20 min)
splitting system is shown in Fig. 1, and analytical Restrictor (FID) :1.1 m × 0.25 mm
conditions are shown in Table 1. Headspace conditions Restrictor (MS) :1.5 m × 0.20 mm
were determined based on USP <467>. The column APC Pressure : 20 kPa
outlet was split between FID and MS, and MS was
performed in scanning mode. Using Shimadzu's FID
Advanced Flow Technology Software to determine the Temp. : 250 °C
splitting ratio, the flowrate ratio was optimized to Make-Up Flowrate : 30 mL/min (He)
FID:MS of 1:1. Hydrogen Flowrate : 40 mL/min
Air Flowrate : 400 mL/min
MS
Ion Source Temp. : 200 °C
Interface Temp. : 250 °C
SCAN Range : m/z 29 to 250
Event Time : 0.3 sec
Splitting Unit

FID

APC Pressure
Control

Fig. 1 System Image