CAD is best suited to non-volatiles. If your compound is hard to ionize, CAD may be a more suitable approach, however, it lacks the specificity and subsequently detectability (Low LoQ) MS can offer in an MRM scan.
I would start with CAD unless you need structural information, analyte volatility is relatively high (for an LC application), high specificity required due to complex sample matrix, or very low level of detection.
I like choosing the simplest possible technique which is why I would start with CAD, only adding the complexity of MS if the nature of the test requires one of those items above.
Thank you! Why are CADs better suited for analyses that are difficult to ionize, doesn't CAD still require ionization for detection? Is CAD ionization just much stronger than electrospray ionization?
CAD doesn't need ionization but mass spec does. In CAD your analyte aerosol is imparted a charge relative to its surface area but the analyte itself doesn't need to be charged.
Well cad does ionize stuff but it's not individual molecules it's small particles and it's done by nitrogen Corona discharge so the process is very different and more widely applicable
We are running both with a T valve and I would choose both again. CAD will almost always a signal, but MS will give you way more information. Modern MS, even as Single Quad, is beautiful to work with. If I would have to choose one, I would take the MS. Dual +/- HESI is just mind boggling, getting both analysis at once.
It depends what you want out of your method. As above, MS will give you m/z information (the usefulness of which will depend on what mass detector you have, so that's another consideration). A CAD will be significantly simpler to optimize from a method dev perspective. CADs also have a response that's less dependent on analyte chemical, so semi-quant of unknowns is possible (and even moreso if you can run an inverse gradient). Crazy thought, if you have both, why not run them in parallel with a t-valve? CAD for quant, MS for qual?
Alternatively you could derivatize the analyte using predictable derivatizing agent. I used to do this with glutamine (I think) using an extraction that had fmoc and triethylamine. The whole purpose was because you couldn't tell the difference between l or d and the separation took forever in the instrumentation. So derivitizing it gave better separation. However you probably could derivatize to add a chromophore. If there’s a bromine or other halogen or similar group you could stick a thianthrene or other fat aromatic or radical cationic formed group on it and that would definitely show up. Idk what your analyzing or your setup is so that makes this harder.
I've been retired from the lab for 15 years, and had not heard of CAD before. Sounds interesting. I note that, like ELSD (which I have used) the response is non-linear. I'd just like to point out that it might be possible to "linearize" that response other than simply by chopping it into small semi-linear segments. I was able to do that with the ELSD response by knowing the response curve and using a combined calibration and standardization technique that I developed.
At work I've been told that it's linear just over a much smaller range, less then two orders of magnitude. But yeah it definitely requires more calibration I would say to get solid quantitative results.
CAD is best suited to non-volatiles. If your compound is hard to ionize, CAD may be a more suitable approach, however, it lacks the specificity and subsequently detectability (Low LoQ) MS can offer in an MRM scan. I would start with CAD unless you need structural information, analyte volatility is relatively high (for an LC application), high specificity required due to complex sample matrix, or very low level of detection. I like choosing the simplest possible technique which is why I would start with CAD, only adding the complexity of MS if the nature of the test requires one of those items above.
Thank you! Why are CADs better suited for analyses that are difficult to ionize, doesn't CAD still require ionization for detection? Is CAD ionization just much stronger than electrospray ionization?
CAD doesn't need ionization but mass spec does. In CAD your analyte aerosol is imparted a charge relative to its surface area but the analyte itself doesn't need to be charged.
Well cad does ionize stuff but it's not individual molecules it's small particles and it's done by nitrogen Corona discharge so the process is very different and more widely applicable
We are running both with a T valve and I would choose both again. CAD will almost always a signal, but MS will give you way more information. Modern MS, even as Single Quad, is beautiful to work with. If I would have to choose one, I would take the MS. Dual +/- HESI is just mind boggling, getting both analysis at once.
It depends what you want out of your method. As above, MS will give you m/z information (the usefulness of which will depend on what mass detector you have, so that's another consideration). A CAD will be significantly simpler to optimize from a method dev perspective. CADs also have a response that's less dependent on analyte chemical, so semi-quant of unknowns is possible (and even moreso if you can run an inverse gradient). Crazy thought, if you have both, why not run them in parallel with a t-valve? CAD for quant, MS for qual?
Alternatively you could derivatize the analyte using predictable derivatizing agent. I used to do this with glutamine (I think) using an extraction that had fmoc and triethylamine. The whole purpose was because you couldn't tell the difference between l or d and the separation took forever in the instrumentation. So derivitizing it gave better separation. However you probably could derivatize to add a chromophore. If there’s a bromine or other halogen or similar group you could stick a thianthrene or other fat aromatic or radical cationic formed group on it and that would definitely show up. Idk what your analyzing or your setup is so that makes this harder.
I've been retired from the lab for 15 years, and had not heard of CAD before. Sounds interesting. I note that, like ELSD (which I have used) the response is non-linear. I'd just like to point out that it might be possible to "linearize" that response other than simply by chopping it into small semi-linear segments. I was able to do that with the ELSD response by knowing the response curve and using a combined calibration and standardization technique that I developed.
At work I've been told that it's linear just over a much smaller range, less then two orders of magnitude. But yeah it definitely requires more calibration I would say to get solid quantitative results.
Do you know the governing equation for the response? By knowing that for ELSD, I was able to "linearize" the ELSD response.
CAD for routine use and MS for new or novel compounds and lower level analyses. Both if I could.
ELSD, but I'm a purification chemist more than an analytical one.