Validated Stability Indicating RP-HPLC Method for Simultaneous Estimation of Codeine Phosphate and Chlorpheniramine Maleate from Their Combined Liquid Dosage Form
The present paper describes the development of quick stability indicating RP-HPLC method for the simultaneous estimation of codeine phosphate and chlorpheniramine maleate in the presence of its degradation products, generated from forced degradation studies. The developed method separates codeine phosphate and chlorpheniramine maleate in impurities/degradation products. Codeine phosphate and chlorpheniramine maleate and their combination drug product were exposed to acid, base, oxidation, dry heat, and photolytic stress conditions, and the stressed samples were analysed by proposed method. The proposed HPLC method utilizes the Shimadzu HPLC system on a Phenomenex C18 column ( , 5？μ) using a mixture of 1% o-phosphoric acid in water？:？acetonitrile？:？methanol (78？:？10？:？12) mobile phase with pH adjusted to 3.0 in an isocratic elution mode at a flow rate of 1？mL/min, at 23°C with a load of 20？μL. The detection was carried out at 254？nm. The retention time of codeine phosphate and chlorpheniramine maleate was found to be around 3.47？min and 9.45？min, respectively. The method has been validated with respect to linearity, robustness, precision, accuracy, limit of detection (LOD), and limit of quantification (LOQ). The developed validated stability indicating HPLC method was found to be simple, accurate, and reproducible for the determination of instability of these drugs in bulk and commercial products. 1. Introduction Codeine phosphate (CP) chemically is 7,8-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol dihydrogen phosphate hemihydrate [1], an alkaloid occurring in Papaver somniferum or obtained from morphine by methylation. The structure of CP is shown in Figure 1(a). It acts as a narcotic analgesic. Figure 1: Chemical structure of (a) codeine phosphate and (b) chlorpheniramine maleate. Chlorpheniramine maleate (CPM) chemically is (RS)-3-(4-chlorophenyl)-3-(pyrid-2-yl) propyl-dimethylamine hydrogen maleate [1] as shown in Figure 1(b). Chlorpheniramine maleate is a first generation alkylamine antihistamine used in the prevention of the symptoms of allergic conditions such as rhinitis and urticaria. The literature survey reveals that many analytical methods are reported for the determination of CP and CPM individually and in combination. The literature survey revealed spectroscopic [2–5] and chromatographic [6–20] methods. The stability of a drug dosage form refers to the ability of a particular form to maintain its physical, chemical, therapeutic, and toxicological specification presented in the monograph on identity, strength, quality, and purity.
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