Abstract:
Objective of the research work was “Development and validation of new analytical
methods for estimation of drugs in combined dosage forms and validation of available
GC method for estimation of diethylamine and 2 Ethyl hexanoic acid”.
Recently, a new combination product (Nuedexta Capsules, Marketed by Avanir
Pharmaceuticals) containing dextromethorphan hydrobromide (DEX) USP 20 mg and
Quinidine Sulphate (QUIN) USP 10 mg has been approved by USFDA in October 2010 and
launched in January 2011. Only one method till date has been reported for simultaneous
estimation of DEX and QUIN in biological fluid using Fluorescence Excitation Method.
Hence, an attempt was made to develop simple, rapid, accurate and precise methods for
simultaneous estimation of the both. Three methods viz., Simultaneous equation,
Derivative and RP-HPLC methods have been successfully developed and validated for
linearity, precision, accuracy, specificity, limit of detection and limit of quantification
according to ICH guidelines.
Simultaneous equation method was performed at 226 nm and 253 nm while first order
derivative at 232.6 and 245 nm in methanolic 0.5 M HCL for DEX and QUIN respectively.
RP-HPLC method was developed with hypersil C8 BDS column using Phosphate Buffer (20
mM) pH 5.5, methanol and acetonitrile in ratio of 50: 40: 10 as mobile phase pumped at flow
rate of 1 ml/min at 221 nm. Beer’s law was obeyed in the range of 5 to 40 ppm for DEX and
2 to 16 ppm for QUIN with r2 0.9991 and 0.9997 for derivative method, 0.9997 and 0.998 for
simultaneous equation and 10 to 50 ppm for DEX and 5 to 25 ppm for QUIN with r2
0.999992 and 0.999995 respectively for RP-HPLC method. All the three methods were
successfully applied to synthetic mixture spiked with standard and % recovery was found
within acceptable range, which indicates potential suitability of the method for routine
analysis of pharmaceutical dosage forms. All the three methods have been validated for other
parameters and from the results, it can be concluded that methods are considered as “valid”.
An attempt was made to develop Q-Ratio Method, but due to very law absorbance at
Isobestic point (at 25 ppm, it showed 0.117 A) and failure to obtain linearity on repetition, the
method was not further exploited.
And available GC methods for estimation of DEA and 2 EHA in ampicillin for injection are
suitable(valid) for its intended use at Astral Pharmaceutical Industries, Vadodara, Gujarat.
