Simultaneous determination of clobutinol hydrochloride and doxylamine succinate from syrups by RP HPLC using a new stationary phase containing embedded urea polar groups

Abstract

A new, simple, fast, reproducible and sensitive reversed phase HPLC method, using a new stationary phase containing embedded urea polar groups, has been developed and validated for the simultaneous determination of clobutinol hydrochloride (CLO) and doxylamine succinate (DOX) in syrups. The determination was carried out on a C8 urea column (125 mm x 3.9 mm i.d., 5 mm particle size) synthetized at the Liquid Chomatography Laboratory (LabCrom) of the Chemistry Institute of Unicamp. The mobile phase consisted of a mixture of acetonitrile:methanol:phosphate buffer (pH 2.5) in the gradient mode. The diode array detector (DAD) was operated at 230 nm for CLO and 262 nm for DOX. The method showed adequate precision, with relative standard deviations (RSD) less than 1%. The presence of the excipients did not interfere in the results of the analysis. Accuracy was determined by adding standards of the drugs to a placebo and good recovery values were obtained. The analytical curves were linear (r 2 0.9999 for CLO and 0.9998 for DOX) over a wide concentration range (2.4-336 μg mL -1 for CLO and 2.3-63 μg mL -1 for DOX). The solutions were stable for at least 72 hours at room temperature. The criteria for validation using the ICH guidelines were fulfilled.Uniterms: Clobutinol hydrochloride/determination. Doxylamine succinate/determination. High performance liquid chromatogralhy/quantitative analysis.Um novo método simples, fácil e reprodutível, de fase reversa para CLAE, usando uma fase estacionária contendo um grupo polar, uréia, embutido, foi desenvolvido e validado para determinação simultânea de cloridrato de clobutinol (CLO) e succinato de doxilamina (DOX) em xarope. A determinação foi realizada em uma coluna C8 uréia (125 mm x 3,9 mm d.i., 5 mm tamanho de partícula) sintetizada em nosso laboratório (LabCrom). A fase móvel consistiu de mistura de acetonitrila:metanol:tampão fosfato pH 2,5, em eluição por gradiente. O detector por arranjos de diodo (DAD) foi utilizado a 230 nm para CLO e a 262 nm para DOX. O método apresentou precisão adequada, com desvio padrão relativo menor que 1%. A presença de excipientes não interferiu nos resultados obtidos. A exatidão foi realizada pela adição dos padrões dos fármacos ao placebo e valores de recuperação aceitáveis foram obtidos. As curvas analíticas mostraram-se lineares (r 2 0,9999 para CLO e 0,9998 para DOX) em uma ampla faixa de concentração (2,4-336 μg mL -1 para CLO e 2,3-63 μg mL -1 para DOX). A solução padrão foi estável por 72 horas a temperatura ambiente. Os parâmetros de validação foram realizados conforme o guia ICH.

Spectroscopic Estimation of Doxylamine Succinate in Tablets and Human Plasma by Formation of Ion-pair Complex

“…An extensive literature survey revealed several spectrophotometric [1][2][3] and chromatographic [4][5][6][7][8][9][10][11][12] methods for estimation of DOX succinate in various dosage forms in individual and combination with other drugs. Majority of reported methods employed with single drug as well as with combinations in different dosage forms, in which no ion-pair spectroscopic approach was developed for analysis in biological samples.…”

Development and Validation of RP-HPLC Method for Simultaneous Estimation of Doxylamine Succinate and Pyridoxine Hydrochloride in Bulk and Pharmaceutical Dosage Forms

“…However, many methods for the estimation of these drugs like UV [1][2][3][4], RP-HPLC [5][6][7], stability indicating HPLC [8] was reported in the literature. But the present method is more sensitive and precise than the reported methods.…”

Development and Validation of a Rapid Chemometrics Assisted RP-HPLC with PDA Detection Method for the Simultaneous Estimation of Pyridoxine HCl and Doxylamine Succinate in Bulk and Pharmaceutical Dosage Form

“…It is an antihistaminic with antimuscarinic and pronounced sedative effect [1][2][3]. Literature survey exposed that there are few UV [1,2,[4][5][6][7] and HPLC [2,[8][9][10][11][12][13][14][15][16][17][18][19]] methods that were reported for these drugs individually and combined with other drugs. There is no article available in the literature regarding chemometrics approach used in the RP-HPLC method development for the simultaneous estimation of PYH and DOX.…”