Development and Validation of Stability-Indicating RP-UPLC Method for the Determination of Methdilazine in Bulk Drug and in Pharmaceutical Dosage Form

A simple, precise, and accurate, and stability-indicating isocratic Ultraperformance Liquid Chromatography (UPLC) method was developed for the determination of methdilazine hydrochloride (MDH) in bulk drug and in its tablets. The use of UPLC, with a rapid 5-minute-reversed-phase isocratic separation on a 1.7？μm reversed-phase packing material to provide rapid ‘‘high throughput’’ support for MDH, is demonstrated. The method was developed using Waters Acquity BEH C18 column (100？mm × 2.1？mm, 1.7？μm) with mobile phase consisting of a mixture of potassium dihydrogenorthophosphate and 1-pentane sulphonic acid buffer of pH 4.0 and acetonitrile (60？:？40 v/v). The eluted compound was detected at 254？nm with a UV detector. The standard curve of mean peak area versus concentration showed an excellent linearity over a concentration range 0.5–80？μg？mL？1 MDH with regression coefficient ( ) value of 0.9999. The limit of detection ( ) was 0.2？μg？mL？1 and the limit of quantification ( ) was 0.5？μg？mL？1. Forced degradation of the bulk sample was conducted in accordance with the ICH guidelines. Acidic, basic, hydrolytic, oxidative, thermal, and photolytic degradations were used to assess the stability indicating power of the method. The drug was found to be stable in acidic, basic, thermal, hydrolytic, and photolytic stress conditions and showed slight degradation in oxidative stress condition. 1. Introduction Methdilazine hydrochloride (MDH), chemically known as (10-[(1-Methyl-3 pyrrolidinyl)methyl]phenothiazine monohydrochloride) [1] (Figure 1), is a synthetic analogue of phenothiazine derivative used as an antihistamine and it is also found to possess antipruritic action [2]. Figure 1: Structure of MDH. The drug is official in United States Pharmacopia [3], which describes UV-spectrophotometric assay in aqueous medium. The literature survey revealed the availability of few methods for the assay of MDH in pharmaceutical formulations. Quantification of MDH has been achieved by high-performance liquid chromatography (HPLC) [4–6], liquid chromatography [7], spectrofluorimetry [8], differential fluorimetry, and differential UV-spectrophotometry [9]. Some visible spectrophotometric methods are also reported for the assay of on pharmaceuticals [10–22]. In recent years, there has been an increasing tendency towards development of stability-indicating assays [23–26], using the approach to stress testing enshrined in International Conference on Harmonisation (ICH) guideline Q2A(R2) [27]. This approach is being extended to pharmaceuticals to enable accurate and precise