HPLC vs. UPLC

In pharmaceutical laboratories and research centers, Liquid Chromatography is the backbone of drug analysis. While High-Performance Liquid Chromatography (HPLC) has been the industry standard for decades, Ultra-Performance Liquid Chromatography (UPLC) is rapidly gaining ground.

Both techniques separate complex mixtures into individual components using a liquid mobile phase, but they are far from identical. This article explores the technical differences, advantages, and why one might be superior to the other.

What is Liquid Chromatography?

Liquid chromatography is an analytical technique used to separate a sample into its individual chemical constituents. It involves a mobile phase (a liquid solvent) that carries the sample through a stationary phase (a column packed with adsorbent material).

As the sample travels through the column, different components move at different speeds, allowing them to be identified and measured by a detector.

Technical Comparison: HPLC vs. UPLC

The shift from HPLC to UPLC represents an evolution in speed, pressure, and efficiency. Below are the primary areas where these two systems differ.

1. Operating Pressure

The most significant difference lies in the pressure capacity of the pumps:

HPLC: Operates at relatively lower pressures, typically between 500 and 6,000 psi.
UPLC: Operates at much higher pressures, reaching up to 15,000 psi (approximately 100 MPa).

This high pressure is the "engine" that allows UPLC to use much smaller particle sizes in its columns without clogging the system.

2. Column Particle Size

The size of the particles inside the chromatography column determines the surface area available for separation:

HPLC: Typically uses a particle size of 5 $\mu m$ .
UPLC: Utilizes much finer particles, often less than 2 $\mu m$ .

Smaller particles provide higher resolution and better separation of the analyte (the substance being measured), but they require the massive pressure mentioned above to push the solvent through.

3. Analysis Speed and Efficiency

Time is money in pharmaceutical manufacturing.

HPLC: A typical run time can range from 15 to 20 minutes.
UPLC: Can deliver the same (or better) separations in just 3 to 10 minutes.

Advantages of UPLC over HPLC

While UPLC is a trademarked technology, the term is often used generally to describe "Extended Performance" chromatography. Its benefits include:

Faster Run Times: Increases laboratory throughput.
Lower Solvent Consumption: Using less liquid reduces costs and is more environmentally friendly.
Superior Sensitivity: Higher peaks and better resolution make it easier to detect trace amounts of impurities.

Comparison Table: HPLC vs. UPLC at a Glance

Feature	HPLC (High Performance)	UPLC (Ultra Performance)
Pressure Range	500 – 6,000 psi	Up to 15,000 psi
Pump Pressure (Metric)	~40 MPa	~100 MPa
Particle Size	5 $\mu m$	< 2 $\mu m$
Analysis Time	15 – 20 Minutes	3 – 10 Minutes
Solvent Use	Higher	Significantly Lower
Industry Status	Most widely used	Growing/Superior performance

Which is Better?

From a purely technical standpoint, UPLC is superior in every way. It is faster, more precise, and uses fewer resources. However, HPLC remains the most widely used technique in the pharmaceutical industry today because of its established protocols and lower initial equipment costs.

If you are entering the pharmaceutical or analytical chemistry field, mastering both is essential. While HPLC is the current workhorse, UPLC is undoubtedly the future of separation science.