Simultaneous detection and quantification of bronchodilators in pure form and from in-vitro drug release of a novel combinational formulation

The analytical method was developed and validated for the quantification of salbutamol sulfate (SS) and ipratropiumbromide (IPB) in accordance with the International Council for Harmonization guidelines in its pure form. Thechromatographic partition was completed utilizing a blend of acetonitrile:phosphate buffer (30:70 v/v) with the pHscale adjusted to 3.0 using o-phosphoric acid at a flow rate of 1 ml/minute in Luna C-18(2)(150 × 4.6 mm i.d., 5 μm)column. The wavelength for detection was fixed at 212 nm. The SS and IPB showed a standard linearity curve in therange of 2–12 µg/ml, with retention time at 2.4 and 3.8 minutes, respectively. The developed method was reported tobe specific, linear (r2 ≥ 0.999), precise at intraday and interday levels (% relative standard deviation < 2.0%), accurate(% recovery: 96.02%–103.62%), and robust. The limit of detection and limit of quantification for SS was found to be0.42 and 1.26 µg/ml, while that of IPB was 0.44 and 1.34 µg/ml, respectively. Additionally, the developed method waseffectively applied in quantifying SS and IPB from its pure, commercial, and in-house prepared transdermal system tounderstanding the in-vitro drug release pattern from patches.

A Novel Spectrophotometric and RP-HPLC methods for Determination of Nortriptyline hydrochloride and Pregabalin in Tablets

A Simple, rapid, specific, accurate, economical and precise UV spectrophotometric and RP-HPLC methods (inaccordance with ICH guidelines) were developed and validated for determination of Nortriptyline hydrochlorideand Pregabalin in tablet dosage form. The first method was based on Q - absorbance ratio, and absorbances ofboth drugs were determined at 239 nm (λmax of Nortriptyline Hydrochloride) and 235 nm (Iso-absorptive Point)when dissolved in methanol. It is found that Pregabalin does not have chromophoric group. To be UV-sensitive,it was compulsory to introduce chromophoric group in Pregabalin structure and make it UV-sensitive. This wasachieved by converting the primary amine group of Pregabalin through reaction with benzoyl chloride to formbenzoylated derivative of Pregabalin. Benzoylated Pregabalin was determined at 225 nm using UV-visiblespectrophotometer. The second method was based on RP-HPLC. The chromatographic separation was performedon an Inertsil ODS C18 column (250 x 4.6mmx 5 μm) with a mobile phase of 0.56 %w/v Sodium hexane sulphonicacid dissolved in water acetonitrile (50:50 %v/v, pH 4.5 adjusted with Glacial Acetic Acid) at flow rate of 1.0mL/min with DAD detection wavelength at 210 nm. Retention times of Nortriptyline Hydrochloride andPregabalin were 7.3894 min and 4.0506 min, respectively. Beer-Lambert’s law obeyed the concentration rangeof 2-12 μg/mL for Nortriptyline Hydrochloride and 10-60 μg/mL for Pregabalin. The results indicated that bothspectrophotometric and RP-HPLC methods were linear, accurate, precise and robust with RSD values less than0.2% and % recovery was within the standard limits (99 - 102%).

Simultaneous estimation of drotaverine hydrochloride and paracetamol in bulk and tablet dosage form by RP-HPLC method.

A simple, rapid, reproducible, accurate and precise Reverse Phase HPLC method was developed for the quantitative simultaneous estimation of Drotaverine hydrochloride and Paracetamol in combined tablet dosage form. Drotaverine hydrochloride is an analog of papaver and is used mainly as an antispasmodic, smooth muscle relaxant. Paracetamol has analgesic and antipyretic activity. The chromatographic separation of both drugs was achieved with 250 x 4.6 mm, i.d 5 μm C-18 column using Methanol: water pH adjusted to 4.0 with O- Phosphoric acid. (60:40 v/v) at the flow rate of 1ml/min. The measurements were made at 243.0 nm using UV detector. The linearity range was found to be 5-80 μg/ml for Drotaverine hydrochloride and 5-70 μg/ml for Paracetamol. The coefficient of correlation for Drotaverine hydrochloride and Paracetamol was found to be 0.9994 and 0.9990 respectively. The retention time for Drotaverine hydrochloride and Paracetamol were 4.562 min and 8.146 min, respectively. The tailing factor for Drotaverine hydrochloride and Paracetamol was found to be 1.12 and 1.18 respectively. The percent recoveries obtained for Drotaverine hydrochloride and Paracetamol were found to be 99.85 and 99.92 respectively. The relative standard deviation for intraday and interday precision in tablet was always less than 2%. The method was validated for linearity, range, precision, accuracy, specificity, selectivity, intermediate precision, ruggedness, robustness, stability and suitability.

Current trends of nonclinical safety evaluation for new drugs / 中国药理学与毒理学杂志

Nonclinical safety evaluation plays a critical role in the process of new drug development.International Conference on Harmonization (ICH) guideline M3 (R2) provides a key direction for the nonclinical safety evaluation process.Proper strategies and toxicological studies should be considered together to move the drug candidates forward efficiently and quickly to support clinical plans and market registration.Updates on ICH guidelines,such as ICH S6 and ICH S9,have great impact on the direction of development.With the increasing cost of development and competition in the industry,elements like predictivity,animal models,and regulatory compliance are also very important in the process.Therefore,an insight into all these factors is essential to toxicologists in the safety evaluation process.The ability to use the overall knowledge will result in a quicker and better new drug development program.