Hi Diogo,
There are a few things that you may want to try here to increase your S/N ratio and increase your LoQ. I don't know what wavelength you're measuring at, but try and increase (or, for your compound, find another) wavelength that your abs is being measured at. HPLC grade solvents will come with a confirmation/quantification on the background noises that they will provide (granted you're buying the quality stuff). You can use their quantification and pick some abs that your compound absorbs well in, as well as one that meets your LoQ standards by the company (HPLC solvent distributor). Look up the grade of your methanol and it's absorbance profile, maybe consider moving to ACN if you're measuring abs at a low (200-250nm) range. Maybe change your solvent supplier. Prepare your solvents as needed, especially if you're quantifying something so low. When preparing your buffers it will also be important to keep them as sterile/uncontaminated as possible. Increasing your resolution will also be important-- I'm not sure what the point of installing the 1500 ul loop as it will simply contribute to band spreading and the flattening of your expected peak and should NOT be used if you want to quantify a chromatographic response. In fact, it would take your sample two minutes to even get through the loop (entirely). If you're injecting a tiny amount over a large volume loop, your resolution will decrease significantly. This will be the same case if you use a large volume with a tiny concentration as some of your sample will, inevitably, be at the end of the loop while the rest could be at the start of the loop. Is your flow correct (not experienced with this size column, but a lower flow can lead to resolution loss).
How long since the HPLC has had schedule maintenance? Contamination (or particulates) can build up on sinker frits, maybe some check valves, injection loops that are changed often, etc. These will all contribute to the noise that is typically seen on a chromatogram.
Sorry for the exhaustive list, I hope some of it can be of some help!
Tyler Smith