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Universal Liquid Chromatography Detector

October 4, 2021 (*UPDATED*)

All liquid chromatographic (LC) detectors used for quantitative measurements exhibit response bias in some way. For example, the ubiquitous UV/Vis detector which is the industry standard will only respond to analytes with chromophores which absorb in the 190-600 nm range, and sensitivity can also be impacted by the wavelength selected for the analysis and the mobile phase properties. Additionally, UV relative response factors (RRF) for analytes within the same sample can often be quite different - requiring the synthesis of authentic reference standards and the determination of correction factors (1/RRF) to allow quantitative assay. Equally, there are known limitations with detectors utilizing mobile phase nebulization towards semi-volatile analytes and linearity of response (e.g. ELSD, CAD, MS). The only LC detector currently recognized as universally responsive, the refractive index (RI) detector, is incompatible with the gradient chromatography typically required for pharmaceutical analysis and is relatively insensitive. All other common detectors also have limitations regarding quantitation.


This ETC project team has several decades of collective experience of working with liquid chromatography and have used or evaluated all current commercially available detectors for their ‘universal’ application with LC. While some detectors show promise, the project team feel that the requirement for unbiased detector response allowing true quantitation irrespective of analyte properties is currently unavailable.  ETC previously issued an RFI in Q4-2020 with the aim of understanding of what technologies are currently being developed within academia and/or industry with a view to either (i) partnering with the group to evaluate the instrument (ii) provide cross-industry insight into any current design or (iii) initiate the development of a new technology which meets the groups requirements.  Using the learnings from the RFI process, ETC is issuing a Request for Proposals (RFP).  

Publication of this RFP is intended to solicit interest in collaborating on the development of a liquid chromatographic detector which is quantitative for all analyte classes.  The scope of this RFP is more narrow than that detailed in the original RFI. The goal of this collaborative project is identify a partner company to work with to develop a prototype instrument with the hope it will become a commercial product in the future.

Download the Request for Proposals (RFP) and submit your response.

Previous RFI Download (Issued Nov 6, 2020)


RFP ISSUED October 4, 2021

QUESTIONS on RFP DUE November 5, 2021 (send via email to address provided in RFP)

RFP RESPONSES DUE November 19, 2021

Q&A Received (Last updated November 17, 2021)

Section 1.6 refers to a project Charter. What is the internal project Charter?  The internal project charter is the agreement signed by all ETC members participating in the project. It provides details about the project (e.g., timelines, costs, deliverables), budget requested, terms/conditions negotiated with the 3rd party.  The Charter serves as the basis for the Development Agreement and Non-Disclosure Agreement between ETC and the 3rd party collaborator.  The Charter, Development Agreement and Non-Disclosure Agreement all use template language which was been reviewed and approved by ETC members to accelerate the process.


Section 2.1 lists possible sponsors. When will the project sponsors be formalized? Will we have direct communication with the project sponsors during the work?  Typically, the project sponsors are known during the scoping phase with the collaborator but will be formalized at the time the project Charter is sent for signature.   For all projects, the 3rd party collaborator has regular meetings with the project sponsors, usually on a monthly or quarterly basis in order to report on progress, receive input/feedback, and get additional information.

What types of support (beyond financial) does the ETC provide?

  • Equipment: HPLC System

  • Staffing: Chemists, Engineers, Software Development

  • Connections within the Pharmaceutical Industry for problem solving


It is unlikely the companies represented by the group members will be able to provide (donate/loan) (U)HPLC’s or other equipment for this development. However, we would be willing to beta-test the detector on-site at their company site and obviously share the data with the collaborator and the ETC team. In this context we could provide access to analytical chemists who can provide feedback on the detector and other aspects e.g. ergonomics. The collaborator would be able to also use the knowledge and experience of the ETC team for problem solving. It is unlikely that the group could provide access to software developers at their companies (and most are unlikely to have these).


General Questions about ETC and the Project

  • Does ETC have a preferred HPLC System? (ie. Waters, Agilent, Thermo)

  • Would we be able to analyze pharmaceutical samples from the project sponsors to compare analyses between detectors?

  • If so, would ETC share analytical data for marketing and white papers? Can we expect to co-author journal articles?

  • Does the ETC group have connections within the ICH Council, or have any crossover

The ETC team represents a number of pharmaceutical companies who have different instruments. However, the detector should ideally be vendor agnostic. The detector should be capable of providing as a minimum an analog output signal and injection triggering (contact closure) with common U/HPLC systems.

Access to proprietary compounds is likely to be company dependent. Certain companies will allow this with a suitable CDA in place, but in some cases, companies would prefer to assess the analytes on site with a beta-test system and share the data back with collaborator. This will be confirmed prior to commencement of any project.

With member consensus, ETC projects have resulted in co-authored presentations and manuscripts. Proprietary compound structures however are unlikely to be publishable unless heavily redacted.

While not all team members have responded, it is unlikely that any members of the team have direct interactions with the ICH. However, we do have colleagues within our respective organizations who could facilitate an interaction if appropriate.

Section 2.3.1 Requirements Table Specific Questions

  • For requirement #2: Sensitive to detection requirements typically required to comply with ICH expectation - Is it possible for you to share the most recent ICH expectations/guidelines that discuss this detection requirement in greater detail? It will help us write a stronger proposal for this request. The requirements are documented in in ICH Q3A(R2), ICH Q3B(R2) and in terms of method validation ICHQ2(R1). The latest versions may be found at ICH Official web site.

  • For requirement #4: Quantitative in terms of response factors - To clarify, is it the desire of ETC to have a detector which looks for the same physiochemical property in all molecules to create a single response factor, that all data can be measured against? Ideally, yes. The detection approach should not be limited to specific, less ubiquitous properties (e.g., must have nitrogen); universal calibration would be highly beneficial.

  • For requirement #5: Quantitative for semi-volatile analytes - If GC Amenable equals Volatile Compounds, then does Non-GC Amenable equal Semi-Volatile Compounds?  Not entirely. As an example, thermally labile volatile compounds are not GC amenable, so the definition is a little more complex. It is known from previous assessment volatility effects were observed with compounds that are typically not volatile with ELSD or CAD - so the phrase ‘semi-volatile’ appears to be detector dependent. A reasonable definition was proposed and could be applied here “Compounds that possess Henry’s law constants (H) in the range of 10^-5 - 3 x 10^-7 atm*m3/mol* and demonstrate higher boiling points, usually greater than that of water with correspondingly low vapor pressure from 10^-14 - 10^-4atm”.

  • For requirement #6: Simple to calibrate - Please define ‘on-board’ standard? Do you require it be built into the system, or just simplistic in its nature?
    Ideally an on-board calibration would be best with a pre-prepared calibrant that can be easily introduced to the system (e.g. could be a refillable vial that is integrated into the detector), but a simple calibration process that is not on-board would also be acceptable. 

  • For requirement #8: Detector response will be independent of changes in mobile phase composition - For clarification, can you list MOBILE PHASE COMPONENTS and ADDITIVES that are widely used in Pharmaceutical LC Analysis? Ex. TOP 10 for this industry – so that we can respond definitively in our proposal. Approximate order of importance:
    1.    Water
    2.    Acetonitrile
    3.    Methanol
    4.    TFA
    5.    Formic acid
    6.    Ammonium hydroxide
    7.    Ammonium acetate
    8.    Phosphate salts i.e. Na+, K+, NH4+
    9.    Ammonium formate
    10.  Acetic acid

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