A simple, fast, sensitive, and accurate spectrophotometric method has been developed for the determination of Chlorpheniramine maleate (CPM) in pure and pharmaceutical dosage forms, The quantitative determination of the drug applied used Zero-crossing order, third-order, and fourth-order derivative which measured at 262 nm,270 nm, and 264nm respectively. The methods obey Beers-Lambert law in the concentration range (1.95-39.07)µg/ml with a relative standard deviation RSD equal to 0.51% for the zero-order and 0.16% for the third-order and 1.94% for the fourth-order when the determination range was (1.95-7.81)µg/ml for the third- order with RSD equal to 1.37% for the integrated area under the positive peak, The developed spectrophotometric method in this study is successfully applied for the direct determination of the pharmaceutical form Histamine, The percentages recoveries were (96-98.6)% for the zero-order, (96.3-103.8) % for the third-order and (96.7-101.6) % for the fourth-order, this method is easy and economical and doesn't require the use of any expensive or toxic reagent; these advantages make it suitable for routine quality control.