Ivermectin and Clorsulon are anthelmintic compounds that are active against types of parasites that are used as an injectable mixture or as a single injectable product for cattle, sheep, horses, and goats. To identify and determine ivermectin and clorsulon as active pharmaceutical ingredients in spiking goat plasma, a linear RP-HPLC method was designed and validated. This approach is precise, simple, accurate, selective, and linear. Separation was performed with a mobile phase composed of a mixture of acetonitrile: ethanol: water (52: 28: 20 v/v %), respectively, at flow rate 1.2 mL/min on column Luna C8 column (4.6 mm, 250 mm, 5µm, 100oA) thermostated at 25o C with UV detection at 254 nm. The diluent is a mixture of mobile phase: methanol (75:25 v/v %). As APIs, the method has been validated for linearity, accuracy, precision, and robustness. The calibration graph was linear in the range of 950-3.8 µg/mL, 50-0.5 µg/mL and 500-1.25 µg/mL for IVMH2B1a, IVM H2B1b and CLR, respectively with regression coefficient (R2) equal 0.999 for each one, with percentage accuracy was 99.42 ± 0.43% for IVM H2B1a, 101.2± 0.05% for IVMH2B1b and 99.46 ± 0.66% for CLR. Among the analytical methods for estimation ivermectin and clorsulon in plasma require a laborious clean-up step on an SPE cartridge; the work is based on simple and rapid liquid-liquid extraction utilizing water-soluble organic solvents. Using a blank plasma sample spiked with IVM and CLR and underwent the method. It was linear in range of 475-2.4 µg/mL, 25-0.5 µg/mL and 250-2.5 µg/mL for IVMH2B1a, IVM H2B1b and CLR, respectively with percentage recovery was 97.98 ± 0.41 %for IVM H2B1a, 97.7 ± 0.15% for IVMH2B1b and 100.27 ± 0.23% for CLR and the intra- and inter-day precision with RSD% did not exceed 2%. Therefore, the proposed method can be used for routine analysis of ivermectin and clorsulon.