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Which N2 Generators should be used for LC-MS/MS?

4 January 2023
  • Nancy Schwartz
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If you are using LC-MS/MS, you are probably using nitrogen for nebulizer/electrospray gas, and possibly for curtain gas, drying gas or collision gas.  Are you using nitrogen from a cylinder and wondering what your other options are? A nitrogen generator can provide you with clean nitrogen 24 hours a day, continuously for a long period of time with very little maintenance. When compared to using cylinders, gas generators can usually pay for themselves within a year or two, so this can be very cost-effective as a long-term solution. The costs are minimal to maintain such systems and usually just include replacing filters.  Many prefer to use generators versus handling bulky gas cylinders. If you need assistance performing a cost comparison for this, please let us know.

Our generators for LC-MS/MS use compressed air to generate nitrogen up to 99.5% purity. The models that appear on our website offer provide maximum flow rates that range from 34 to 75 L/min, as shown below. However, additional models are available as custom products, which would not appear on our website. These models might offer higher max. flow rates or perhaps a built-in air compressor, for example.


We do suggest pairing one generator with one/each LC-MS/MS system for best performance.  So, how do you choose the best generator model for your LC-MS/MS system? The key factors are purity and flow rate, which are listed by the instrument manufacturer. We suggest choosing a generator that produces the needed purity and provides at least 10% more than the flow rate suggested by the LC-MS/MS manufacturer. A secondary consideration is the desired outlet pressure, which is also given by the instrument manufacturer. Below we have these specifications listed for each model.


You may wonder why the purities above show a range in the above specifications. This is because the flow rate and pressure both influence the purity. To give you some idea of how this works, for example, in the manual we show a table below that applies to Model N2-14 (our catalog number 20677):


Continuing further with an example inquiry, let’s say for example the analyst has a Waters™ Xevo TQ MS. Gas requirements are listed here by Waters WKB4039_What_are_the_gas_requirements_for_a_Xevo_TQ_MS

Key information from the above link for this instrument:

  • The Xevo TQ MS requires a supply of dry, oil-free nitrogen with a purity of at least 95%.
  • The nitrogen must be regulated at 6.75 ±0.25 bar (98 ±4 psi) outlet pressure, using a two-stage gas regulator with an appropriate outlet range, for example, 0 to 11 bar (0 to 160 psi).
  • During API operation, typical nitrogen usage varies from 600 to 1200 L/h (at atmospheric pressure). 
  • Argon is required for the collision cell. (So, this means the required flow for collision does not factor into the total flow of nitrogen needed. Only the flow for API needs to be considered.)

From the above table, we can see that a purity of 95% is easily obtained by Model N2-14.

To meet the requirement of 98 ±4 psi outlet pressure, we can see that up to 100 psi can be achieved at purities ranging from 95-99.5%, corresponding to 8.1- 42.0 SLPM (standard litre per minute).

To meet the requirement of up to 1200 L/hour (=20 L/min), at an outlet pressure of 100 psi, a purity close to 98.0% would be achieved, as listed for 20.5 SLPM.  A higher flow could be used, but purity decreases accordingly. They could operate with a flow of 27.6 SLPM and achieve purity of 97.0%, or they could increase flow further to 34.4 SLPM, which would result in a purity of 96.0%. If they really wanted to provide the highest flow possible at 100 psi, they could increase to 42.0 SLPM, which would result in 95.0% which is their minimum purity requirement.

Let’s consider if the customer wants to operate at 125 psi rather than 100 psi, since 100 is a minimum requirement. Under that scenario, we move to the next set of columns in the table. At a flow of 25.7 SLPM, they can achieve a purity of 98.0%. The highest flow they could possibly use is 52.7 SLPM, which results in a 95% purity, which is the minimum requirement for this instrument.


Moving on to another topic here, you might notice that we also sell a Nitrogen generator for GC use instead of LC, which is our catalog number 20697. Occasionally we are asked if catalog number 20697 would work for LC-MS/MS. If you look at the description for catalog number 20697, the maximum outlet flow is 1100 cc/min= 1.1 L/min, versus a range of 34-75 L/min that is typically required for LC-MS/MS instruments. The flow simply is not high enough, although the higher purity is perfect for GC purposes.

I hope you find this information helpful in selecting a nitrogen generator for your LC-MS/MS system(s).

Thank you for reading.

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