ntroduction: Clarithromycin is a macrolide antibiotic that is active against a variety of microorganisms. It is widely used in the local and international market in different pharmaceutical dosage forms. However, its chemical structure lacks a chromophore and hence it has a low absorption and this makes it more difficult to be detected at low concentrations. In this research project, we proposed an easy and feasible chemical derivatization of clarithromycin to introduce a chromophore in order to increase its absorptivity at low concentration using a simple reverse phase HPLC analytical method. Methodology: Chemical derivatization of clarithromycin involved an introduction of benzoyl groups as a chromophore through esterification reaction. A reverse phase analytical HPLC method was developed to quantify clarithromycin at a very low concentration compared to the standard official pharmacopeia.Results: Clarithromycin was successfully derivatized and a hyperchromic and bathochromic shift to UV absorption lambda max (λmax) was achieved (λmax = 245nm.) A successful chromatographic separation was obtained using reverse phase HPLC chromatography. The developed method was capable of detecting and quantifying clarithromycin at very low concentration. The Limit of Quantification (LOD) and Limit of Quantification (LOQ) was found to be 2*10-8 mg/ml and 2*10-6 mg/ml respectively.Conclusion: Clarithromycin was successfully derivatized to a chromophore containing molecule. The developed reverse phase HPLC method is capable to detect and quantify clarithromycin at a very low concentration. The method can successfully quantify clarithromycine when present in low concentration such as in biological and enviromental samples.