Choosing the right buffers and solvents is critical in LC-MS because the entire mobile phase directly enters the mass spectrometer. Compatibility with the ionization source (like ESI or APCI) is essential for high-quality data.

1. Why Volatile Buffers are Essential
Non-volatile salts, such as phosphate buffers, are unsuitable for LC-MS. As the mobile phase evaporates, these salts leave a residue that can:

Contaminate and clog the ion source.

Cause signal suppression.

Increase background noise.

Necessitate frequent and costly maintenance.

Volatile buffers are the solution. They provide stable pH control while being easily removed in the gas phase.

Benefits of Volatile Buffers:

High Sensitivity: They evaporate cleanly, allowing analytes to ionize efficiently without interference.

Low Background: Complete evaporation minimizes background ions, leading to a cleaner spectrum and better signal-to-noise.

System Stability: They prevent the residue buildup that plagues systems using non-volatile salts.

Common Volatile Buffers:

Ammonium Acetate (pH range ~4-6)

Ammonium Formate (pH range ~3-6)

Formic Acid / Acetic Acid (for acidic conditions)

Ammonium Hydroxide (for basic conditions)

2. Why Non-Polar Solvents Should Be Avoided
The choice of organic modifier is equally important. Non-polar solvents (like hexane or toluene) are not recommended for typical reversed-phase LC-MS for several reasons:

Poor Miscibility: Most LC-MS mobile phases are aqueous. Non-polar solvents are immiscible with water, which can cause phase separation.

Low Volatility & Unstable Spray: They do not evaporate efficiently in the MS source, leading to an unstable spray, a noisy baseline, and system contamination.

Ion Suppression: Their low dielectric constant is not conducive to good ion formation in ESI, resulting in poor signal intensity.

Safety Concerns: They often have higher toxicity and flammability.

3. Preferred Solvents for LC-MS
The most commonly used solvents are polar and volatile, such as Methanol and Acetonitrile.

These are ideal because they are:

Fully miscible with water.

Highly volatile, ensuring easy removal in the ion source.

Able to produce stable electrospray droplets, which promotes efficient ionization.

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Gas Chromatography (GC) is a powerful analytical technique widely used to separate and analyze volatile organic compounds across a variety of sample types.

How It Works:
In GC, a vaporized sample is introduced into a column filled with a stationary phase. An inert carrier gas (like helium or nitrogen) propels the sample through the column. Compounds move at different rates depending on their chemical properties, allowing for effective separation and detection.

Common Applications of GC:

Monitoring organic contaminants in drinking water

Analyzing fuels and petroleum derivatives

Detecting pesticide residues in food products

Supporting pharmaceutical analysis and forensic investigations

⚙️ Core Components of a GC System:

Sample injection unit

Separation column (often coiled and housed in a temperature-controlled oven)

Detector (typically FID or TCD)

Temperature regulation system

Data acquisition system (generating chromatograms)

Why Use GC?
Gas Chromatography delivers excellent sensitivity and precision, making it indispensable for research, environmental analysis, and quality assurance. Effective use requires careful sample prep, method optimization, and data interpretation.

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Suppose this in residual sample method
Method -1
Here, methanol specification =NMT 1000 ppm

Standard concentration=0.1 mg/ml
Sample concentration=100 mg/ml

Calculation for 100% metlanol respect to sample=(0.1*1000000)/100=1000 ppm

Method:2
Specification methanol= NMT 1000 ppm
=1000 mg/L=0.1%
Sample concentration=100 mg/ml

Calculation methanol 100% respect to sample =100 mg/ml0.1%=(100*0.1)/100=0.1mg/ml=100 ppm

Why 10 time difference between two methods?

Hello,
I am running an impurity analysis method for DMSO with the following parameters:

FID Temperature: 250 °C
Injector Temperature: 250 °C
Column: Agilent DB-624
Flow: 5 mL/min (Hydrogen)
Initial temp: 100 °C, hold for 2 min
Ramp from 100 to 200 °C at 10 °C/min
Final temp: 200 °C, hold for 3 min
Injection volume: 0.5 microliters
Injection syringe volume: 1 microliter (auto-injector)
Split: 1:10
Liner: Ultrainert 5190-2295
FID flows:
• Hydrogen: 35 mL/min
• Air: 400 mL/min
• Nitrogen: 35 mL/min

I’m having serious issues with area repeatability when injecting the same vial 6 times in a row. I’m getting %RSD values around 9%, and my requirement is ≤ 5.0%
I’ve tried all kinds of adjustments—changing injection speeds, adding a 3-second viscosity delay… but nothing seems to solve the issue.

Can you help me?

Thank you very much.

I was running a sequence of product samples and decided to inject a methanol blank in between. To my surprise, I saw unexpected peaks—some of which matched my analytes.

In a long GC run (about 30 samples), I noticed that retention times started shifting gradually. Early samples were fine, but later ones drifted.