Introduction
Analysis of residual solvent is a critical application in the pharmaceutical industry.
The choice of solvent during manufacturing can improve yield or typically affect the
chemical properties of the product synthesized. However, solvents do not enhance
the product’s efficacy, and must be removed as completely as possible to meet
product specifications and good manufacturing practices
1
. Therefore, testing for
residual solvents during production or purification processes is a necessary aspect of
manufacturing.
Analysis of residual solvents according to USP 467 was evaluated on an
AgilentIntuvo system equipped with a headspace sampler. The Agilent Intuvo 9000
Gas Chromatograph yields advantages over conventional GC systems:
• Modular flow path for simplified sample splitting to two columns
• Quick column changes for easier method development
• Smaller footprint
USP 467
ANALYSIS OF RESIDUAL SOLVENTS
Technology Advantage: Agilent Intuvo 9000 GC with HS
For more information, visit:
www.agilent.com
Instrument conditions.
Parameter Value
Agilent Intuvo 9000 GC
Inlet 140 °C Split 5:1
Column Agilent J&W DB-Select 624 Ultra Inert Intuvo, 30 m × 0.32 mm, 1.8 µm
(p/n 123-0334UI-INT)
Column flow 2 mL/min
Oven 40 °C (5 minutes) then 15 °C/min to 180 °C (3 minutes)
Jumper chip 250 °C
FID 250 °C
Agilent 7697A Headspace Sampler
Oven 85 °C
Loop 85 °C
Transfer line 100 °C
Vial equilibration 40 minutes
Injection duration 0.5 minutes
Vial 10 mL
Shaking On, level 2
Vial fill flow 50 mL/min
Vial fill pressure 15 psi
Vial pressure equilibration time 0.05 minutes
Loop fill ramp rate 20 psi/min
Final loop pressure 10 psi
Loop equilibration 0.05 minutes
Experimental
An Intuvo 9000 GC was equipped with an Agilent 7697A Headspace Sampler.
Class1, Class 2a, and Class 2b standard solutions were prepared and evaluated
according to USP 467 methodology.