Chromatography Forum

Hi, we are trying to determine the residual solvents Diisopropyl ethylamine, Dimethyl Sulfoxide methanol, methylene chloride, n-butyl Acetate, n-Hexane, Triethylamine and Toluene in ***** drug substance. The column is DB-5. We are using an Agilent 7694 Headspace Sampler with fixed 1mL sample loop and Agilent 6890 Flame Ionization Detector.

Solvents were dissolved and made to volume in DMSO originally, but we had poor recoveries and carryover, so we changed the solvent to 1% Ammonium Hydroxide, 4% water, 95% DMSO). We saw improved recoveries for everything except hexane, which shows recoveries <90 % on the standard.

Ive added the gc+hs conditions.

Zone Temperatures: Oven 80 °C, Loop 120 °C, Transfer Line Temperature 170 °C
GC Cycle Time 40.0 min, Vial Equilibration Time 45.0 min
Pressurization Time 0.50 min, Inject Time 1.0 min, Vial Pressure 10 psi

Volatile Inlet, Injection Mode: Split, Carrier Gas: Helium, Temperature: 180°C, Split Ratio: 20:1

The separation uses a gradient oven temperature program:
Initial Temperature is 50°C which is held for 15 mins
Ramp 1 IS 10°C/min until 200°C which is held for 3 mins
The post-run equilibration time is 1 min and the total Run Time is 33 min.
Carrier Flow: 3.9 mL/min

Any ideas how to improve the recovery of hexane?
Thanks
Martina

How are you determining your recoveries?

If you are comparing an external std versus the same solution containing your drug any 'recoveries' may be higher than 100% or less than 100% depending upon the analyte and solvent solution used.

best wishes,

Rod