\documentclass[twocolumn,twoside]{article}
\makeatletter\if@twocolumn\PassOptionsToPackage{switch}{lineno}\else\fi\makeatother

\usepackage{amsfonts,amssymb,amsbsy,latexsym,amsmath,tabulary,graphicx,times,xcolor}

%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
% Following additional macros are required to function some 
% functions which are not available in the class used.
%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
\usepackage{url,multirow,morefloats,floatflt,cancel,tfrupee}
\makeatletter


\AtBeginDocument{\@ifpackageloaded{textcomp}{}{\usepackage{textcomp}}}
\makeatother
\usepackage{colortbl}
\usepackage{xcolor}
\usepackage{pifont}
\usepackage[nointegrals]{wasysym}
\urlstyle{rm}
\makeatletter

%%%For Table column width calculation.
\def\mcWidth#1{\csname TY@F#1\endcsname+\tabcolsep}

%%Hacking center and right align for table
\def\cAlignHack{\rightskip\@flushglue\leftskip\@flushglue\parindent\z@\parfillskip\z@skip}
\def\rAlignHack{\rightskip\z@skip\leftskip\@flushglue \parindent\z@\parfillskip\z@skip}

%Etal definition in references
\@ifundefined{etal}{\def\etal{\textit{et~al}}}{}


%\if@twocolumn\usepackage{dblfloatfix}\fi
\usepackage{ifxetex}
\ifxetex\else\if@twocolumn\@ifpackageloaded{stfloats}{}{\usepackage{dblfloatfix}}\fi\fi

\AtBeginDocument{
\expandafter\ifx\csname eqalign\endcsname\relax
\def\eqalign#1{\null\vcenter{\def\\{\cr}\openup\jot\m@th
  \ialign{\strut$\displaystyle{##}$\hfil&$\displaystyle{{}##}$\hfil
      \crcr#1\crcr}}\,}
\fi
}

%For fixing hardfail when unicode letters appear inside table with endfloat
\AtBeginDocument{%
  \@ifpackageloaded{endfloat}%
   {\renewcommand\efloat@iwrite[1]{\immediate\expandafter\protected@write\csname efloat@post#1\endcsname{}}}{\newif\ifefloat@tables}%
}%

\def\BreakURLText#1{\@tfor\brk@tempa:=#1\do{\brk@tempa\hskip0pt}}
\let\lt=<
\let\gt=>
\def\processVert{\ifmmode|\else\textbar\fi}
\let\processvert\processVert

\@ifundefined{subparagraph}{
\def\subparagraph{\@startsection{paragraph}{5}{2\parindent}{0ex plus 0.1ex minus 0.1ex}%
{0ex}{\normalfont\small\itshape}}%
}{}

% These are now gobbled, so won't appear in the PDF.
\newcommand\role[1]{\unskip}
\newcommand\aucollab[1]{\unskip}
  
\@ifundefined{tsGraphicsScaleX}{\gdef\tsGraphicsScaleX{1}}{}
\@ifundefined{tsGraphicsScaleY}{\gdef\tsGraphicsScaleY{.9}}{}
% To automatically resize figures to fit inside the text area
\def\checkGraphicsWidth{\ifdim\Gin@nat@width>\linewidth
	\tsGraphicsScaleX\linewidth\else\Gin@nat@width\fi}

\def\checkGraphicsHeight{\ifdim\Gin@nat@height>.9\textheight
	\tsGraphicsScaleY\textheight\else\Gin@nat@height\fi}

\def\fixFloatSize#1{}%\@ifundefined{processdelayedfloats}{\setbox0=\hbox{\includegraphics{#1}}\ifnum\wd0<\columnwidth\relax\renewenvironment{figure*}{\begin{figure}}{\end{figure}}\fi}{}}
\let\ts@includegraphics\includegraphics

\def\inlinegraphic[#1]#2{{\edef\@tempa{#1}\edef\baseline@shift{\ifx\@tempa\@empty0\else#1\fi}\edef\tempZ{\the\numexpr(\numexpr(\baseline@shift*\f@size/100))}\protect\raisebox{\tempZ pt}{\ts@includegraphics{#2}}}}

%\renewcommand{\includegraphics}[1]{\ts@includegraphics[width=\checkGraphicsWidth]{#1}}
\AtBeginDocument{\def\includegraphics{\@ifnextchar[{\ts@includegraphics}{\ts@includegraphics[width=\checkGraphicsWidth,height=\checkGraphicsHeight,keepaspectratio]}}}

\DeclareMathAlphabet{\mathpzc}{OT1}{pzc}{m}{it}

\def\URL#1#2{\@ifundefined{href}{#2}{\href{#1}{#2}}}

%%For url break
\def\UrlOrds{\do\*\do\-\do\~\do\'\do\"\do\-}%
\g@addto@macro{\UrlBreaks}{\UrlOrds}



\edef\fntEncoding{\f@encoding}
\def\EUoneEnc{EU1}
\makeatother
\def\floatpagefraction{0.8} 
\def\dblfloatpagefraction{0.8}
\def\style#1#2{#2}
\def\xxxguillemotleft{\fontencoding{T1}\selectfont\guillemotleft}
\def\xxxguillemotright{\fontencoding{T1}\selectfont\guillemotright}

\newif\ifmultipleabstract\multipleabstractfalse%
\newenvironment{typesetAbstractGroup}{}{}%

%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%

\usepackage[authoryear]{natbib}



\newif\ifnokeywords\nokeywordsfalse

\makeatletter\input{size10-pointfive.clo}\makeatother%
\definecolor{kwdboxcolor}{RGB}{242,242,242}
\usepackage[hidelinks,colorlinks=true,allcolors=blue]{hyperref}
\linespread{1}                 
\def\floatpagefraction{0.8}

\usepackage[paperheight=11.69in,paperwidth=8.26in,top=1in,bottom=1in,left=1in,right=.75in,headsep=24pt]{geometry}

\usepackage{multirow-custom}

\makeatletter

\def\hlinewd#1{%
  \noalign{\ifnum0=`}\fi\hrule \@height #1%
  \futurelet\reserved@a\@xhline}
\def\tbltoprule{\hlinewd{1pt}\\[-14pt]}
\def\tblbottomrule{\noalign{\vspace*{6pt}}\hline\noalign{\vspace*{2pt}}}
\def\tblmidrule{\hline\noalign{\vspace*{2pt}}}



\let\@articleType\@empty
\let\@journalDoi\@empty
\let\@journalVolume\@empty
\let\@journalIssue\@empty
\let\@crossMarkLink\@empty
\let\@receivedDate\@empty
\let\@acceptedDate\@empty
\let\@revisedDate\@empty
\let\@publishedDate\@empty
\let\@copyrightYear\@empty
\let\@firstPage\@empty
\def\articleType#1{\gdef\@articleType{#1}}
\def\journalDoi#1{\gdef\@journalDoi{#1}}
\def\crossMarkLink#1{\gdef\@crossMarkLink{#1}}
\def\receivedDate#1{\gdef\@receivedDate{#1}}
\def\acceptedDate#1{\gdef\@acceptedDate{#1}}
\def\revisedDate#1{\gdef\@revisedDate{#1}}
\def\publishedDate#1{\gdef\@publishedDate{#1}}
\def\copyrightYear#1{\gdef\@copyrightYear{#1}}
\def\journalVolume#1{\gdef\@journalVolume{#1}}
\def\journalIssue#1{\gdef\@journalIssue{#1}}
\def\firstPage#1{\gdef\@firstPage{#1}}
\let\@issuelogo\@empty%
\let\@issuelogoex\@empty%
\def\issuelogo#1{\gdef\@issuelogo{#1}}
\def\issuelogoex#1{\gdef\@issuelogoex{#1}}


\def\author#1{%
  \gdef\@author{%
    \hskip-\dimexpr(\tabcolsep)\hskip5pt%
    \parbox{\dimexpr\textwidth-1pt}%
    {\fontsize{11}{13}\selectfont\raggedright #1}%
  }%
}


\usepackage{pharmascope-abs}
\usepackage{caption}
\usepackage{lastpage}
\usepackage{fancyhdr}
\usepackage[noindentafter,explicit]{titlesec}
\usepackage{fontspec}

\setmainfont[%
BoldFont=cambriab.ttf,%
ItalicFont=CAMBRIAI.TTF,%
BoldItalicFont=CAMBRIAZ.TTF]{Cambria.ttf}
\lefthyphenmin = 3

\def\title#1{%
  \gdef\@title{%
      \vspace*{-40pt}%
       \ifx\@articleType\@empty\else{\fontsize{10}{12}\scshape\selectfont\hspace{8pt}\@articleType\hfill\mbox{}\par\vspace{2pt}}\fi%
       \minipage{\linewidth}
         \hrulefill\\[-0.7pt]%%{\includegraphics[width=75pt,height=50pt]{ijrps_logo.png}}\hfill
         \mbox{~}\hspace{5pt}\parbox{.1\linewidth}{\IfFileExists{images/\@issuelogo.\@issuelogoex}{\includegraphics[width=79pt,height=61pt]{images/\@issuelogo.\@issuelogoex}}{\includegraphics[width=75pt,height=50pt]{ijrps_logo.png}}}\hfill
         \fcolorbox{kwdboxcolor}{kwdboxcolor}{\parbox{.792\linewidth}{%
          \begin{center}\fontsize{17}{17}\selectfont\scshape\vskip-7pt International Journal of Research in Pharmaceutical Sciences\hfill\end{center}%
          \vspace*{-10pt}\hspace*{4pt}{\fontsize{8}{9}\selectfont Published by JK Welfare \& Pharmascope Foundation\hfill  Journal Home Page: \href{https://ijrps.com}{\color{blue}\underline{\smash{https://ijrps.com}}}}\hspace*{4pt}\mbox{}}}%
       \par\vspace*{-1pt}\rule{\linewidth}{1.3pt}%
       \endminipage%
    \par\vspace*{9.2pt}\parbox{.98\linewidth}{\linespread{.9}\raggedright\fontsize{14}{17}\selectfont #1}%
    \vspace*{-8pt}%
  }
}


\setlength{\parindent}{0pt}
\setlength{\parskip}{0.4pc plus 1pt minus 1pt}

\def\abbrvJournalTitle{Int. J. Res. Pharm. Sci.}

\fancypagestyle{headings}{%
  \renewcommand{\headrulewidth}{0pt}%
  \renewcommand{\footrulewidth}{0.3pt}
  \fancyhf{}%
  \fancyhead[R]{%
    \fontsize{9.12}{11}\selectfont\RunningAuthor,\ \abbrvJournalTitle,\ \ifx\@journalVolume\@empty X\else\@journalVolume\fi%
    \ifx\@journalIssue\@empty\else(\@journalIssue)\fi%
    ,\ \ifx\@firstPage\@empty 1\else\@firstPage\fi-\pageref*{LastPage}%
  }%
  \fancyfoot[LO,RE]{\fontsize{9.12}{11}\selectfont\textcopyright\ International Journal of Research in Pharmaceutical Sciences}%
  \fancyfoot[RO,LE]{\fontsize{9.12}{11}\selectfont\thepage}
}\pagestyle{headings}

                                                         
\fancypagestyle{plain}{%
  \renewcommand{\headrulewidth}{0pt}%
  \renewcommand{\footrulewidth}{0.3pt}%
  \fancyhf{}%
  \fancyhead[R]{%
    \fontsize{9.12}{11}\selectfont\RunningAuthor,\ \abbrvJournalTitle,\ \ifx\@journalVolume\@empty X\else\@journalVolume\fi%
    \ifx\@journalIssue\@empty\else(\@journalIssue)\fi%
    ,\ \ifx\@firstPage\@empty 1\else\@firstPage\fi-\pageref*{LastPage}%
  }%
  \fancyfoot[LO,RE]{\fontsize{9.12}{11}\selectfont\textcopyright\ International Journal of Research in Pharmaceutical Sciences}%
  \fancyfoot[RO,LE]{\fontsize{9.12}{11}\selectfont\thepage}
  \ifx\@firstPage\@empty\else\setcounter{page}{\@firstPage}\fi
}


\def\NormalBaseline{\def\baselinestretch{1.1}}
\usepackage{textcase}
\setcounter{secnumdepth}{0}

\titleformat{\section}[block]{\bfseries\boldmath\NormalBaseline\filright\fontsize{10.5}{13}\selectfont}
{\thesection}
{6pt}
{\MakeTextUppercase{#1}}
[]
\titleformat{\subsection}[block]{\bfseries\boldmath\NormalBaseline\filright\fontsize{10.5}{12}\selectfont}
{\thesubsection}
{6pt}
{#1}
[]
\titleformat{\subsubsection}[block]{\NormalBaseline\filright\fontsize{10.5}{12}\selectfont}
{\thesubsubsection}
{6pt}
{#1}
[]
\titleformat{\paragraph}[block]{\NormalBaseline\filright\fontsize{10.5}{10}\selectfont}
{\theparagraph}
{6pt}
{#1}
[]
\titleformat{\subparagraph}[block]{\NormalBaseline\filright\fontsize{10.5}{12}\selectfont}
{\thesubparagraph}
{6pt}
{#1}
[]

\titlespacing{\section}{0pt}{.5\baselineskip}{.5\baselineskip}  
\titlespacing{\subsection}{0pt}{.5\baselineskip}{.5\baselineskip}  
\titlespacing{\subsubsection}{0pt}{.5\baselineskip}{.5\baselineskip}  
\titlespacing{\paragraph}{0pt}{.5\baselineskip}{.5\baselineskip}  
\titlespacing{\subparagraph}{0pt}{.5\baselineskip}{.5\baselineskip}

\captionsetup[figure]{skip=1.4pt,font=bf,labelsep=colon,justification=raggedright,singlelinecheck=false}
\captionsetup[table]{skip=1.4pt,font=bf,labelsep=colon,justification=raggedright,singlelinecheck=false}

\def\bibyear#1{#1}
%\def\bibjtitle#1{#1}   %%Publisher request
\def\bibauand{}
\setlength\bibsep{3pt}
\setlength\bibhang{8pt}

\makeatother
\date{}


\usepackage{float}

\begin{document}


\def\RunningAuthor{H. N. K. AL-Salman et al.}
\firstPage{3461}
\articleType{Original Article}
\receivedDate{05.03.2019}
\acceptedDate{06.06.2019}
\revisedDate{02.06.2019}
\journalVolume{10}
\journalIssue{4}
\journalDoi{ijrps.v10i4.1663}
\copyrightYear{2019}
\def\authorCount{4}
\def\affCount{3}

\def\journalTitle{International Journal of Research in Pharmaceutical Sciences}

\title{The development of analytical methods to determine metoclopramide-hydrochloric acid in the standard raw and it compared with pharmaceuticals}
\author{Khawla~Salman~Abd-Alrassol\textsuperscript{1},  
            Qutaiba~A.~Qasim\textsuperscript{2},  
            Maitham~Ali~AL-Rikabi\textsuperscript{3}, 
            H.~N.~K.~AL-Salman\textsuperscript{*}\textsuperscript{1}~\\[5pt]{\textsuperscript{1}Department of pharmaceutical chemistry\unskip, College of pharmacy, Basrah University, Iraq}~\\{\textsuperscript{2}Department of Clinical Laboratory Sciences\unskip, College of pharmacy, Basrah University, Iraq}~\\{\textsuperscript{3}Department of Clinical Pharmacy\unskip, College of pharmacy, Basrah University, Iraq  }}

\begin{abstract}
The three novel easy, to the prepare and sensitive spectral methods, were used to estimate metoclopramide in both standard and pharmaceuticals. The effective double{\textendash}electron, was present in the metoclopramide compound helps to interact in an acidic medium with a reagent such as diazetide resorcinol and 8-hydroxyquinoline reagents. The present article was extended to find out three analytical methods with UV-V is the detector. In both A and B methods, two azo-dyes are formed, they are orange-red and red stable and have high water solubility, giving highest absorption values at 415 nm and 485 nm but the C method will depend on a complex colour configuration with the p-benzoquinone reagent, which has a maximum absorption at a wavelength of 285 nm. Beer's law was applied in a range of concentrations between 1 and 10 \ensuremath{\mu }g / ml, 2-20 \ensuremath{\mu }g / ml and 1-30 \ensuremath{\mu }g / ml. The values of the molar absorption factors were (4.1224 \ensuremath{\times} 104, 3.0229 \ensuremath{\times} 104 and 1.7373 \ensuremath{\times} 104) L mol-1cm-1 with a sensitivity of Sandell's equal to 0.2606 \ensuremath{\times} 10-4, 0.9834 \ensuremath{\times} 10-4 and 0.2568 \ensuremath{\times} 10 - 4 \ensuremath{\mu }g cm-2 to methods A, B respectively and LLOD values were 0.255, 0.553 and 0.158 \ensuremath{\mu }g / ml to methods A, B and C. LLOQ 0.512, 0.898 and 0.455 \ensuremath{\mu }g / ml to methods A, B, C respectively. The constant fixed Kf configuration was also calculated for the colored outputs of the reaction where it was found to be equal to 43.6435 \ensuremath{\times} 108, 54.6261 \ensuremath{\times} 10-8 and 17.29099 \ensuremath{\times} 106 L2 mol-2 to all methods A, B, C respectively. The values of G were calculated based on -43.9293 KJ / mol, -44.3735 and -51.2019. G values, molar absorption factor, Sandell sensitivity, detection limit.
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}metoclopramide-HCl,\newline coupling reaction,\newline complex formation,\newline spectrophotometric studies,\newline stability constants
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ H.~N.~K.~AL-Salman~\\ Phone:\ +9647702683703~\\  Email:\ hsennaserh@yahoo.com
        \par}\vspace*{-11pt}\hrulefill\par{\fontsize{12}{14}\selectfont ISSN: 0975-7538}\par% 
        \textsc{DOI:}\ \href{https://doi.org/10.26452/\@journalDoi}{\textcolor{blue}{\underline{\smash{https://doi.org/10.26452/\@journalDoi}}}}\par%
        \vspace*{-11pt}\hrulefill\\{\fontsize{9.12}{10.12}\selectfont Production and Hosted by}\par{IJRPS |~\href{https://ijrps.com}{https://ijrps.com}}\par%
        \vspace*{-2pt}{\fontsize{9.12}{10.12}\selectfont\textcopyright\ \@copyrightYear\ $|$ All rights reserved.}\par%
        \vspace*{-11pt}\rule{\linewidth}{1.2pt}
        \makeatother
        
    
\section{Introduction}
The chemical formula to metoclopramide hydrochloride, C\ensuremath{_{14}}, \ensuremath{\Delta }H, Cl, N, O. HCl with molecular weight (354.3 gm /mol) the scientific name under the IUPAC system is 4-amino-5-chloro-N-(2-diethylamino) ethyl-2 ethlyI-2 ethyl-2). Figure~\ref{f-d8aa01567cbb} shows the structural form of hydrochloride metoclopramide. Metoclopramide hydrochloride is an odourless white crystalline powder. 1 mg of metoclopramide is soluble in 0.7 gm of water at 25 C, and 3 gm of it is soluble in ethanol (96\%), 55 gm in chloroform (90\%) and soluble in diluted hydrochloric acid which is practically soluble in ether. Metoclopramide hydrochloride contains ionization constants with values of 0.42 (pK\ensuremath{_{1}}) and 9.71(pK\ensuremath{_{2}}) \unskip~\citep{571314:13185961,571314:13185962,571314:13185963,571314:13185964,571314:13185965}. Metoclopramide strengthens the oesophagal muscle of the oesophagus and reduces gastric acid reflux. Metoclopramide hydrochloride is used to reduce nausea and vomiting   when combined with chemotherapy, and it speeds up gastric emptying of harmful intestinal and liquid meals. It is an alternative benzamide drug that is used, because of its Kinetic properties to reduce disorders of gastrointestinal degeneration, such as ileal motility, stomach, oesophagus and reduce indigestion, vomiting and nausea \unskip~\citep{571314:13185966,571314:13185967,571314:13185968}. Metoclopramide hydrochloride has been used because of its pro-gastrointestinal effects through cholinergic stimulation of gastrointestinal diseases caused by radiotherapy, chemotherapy and postoperative nausea. Several analytical methods were used to determine metoclopramide hydrochloride, such as High{\textendash}performance liquid chromatography, gas chromatography, voltage measurement, voltage measurement method, chemical fluorescence. Metoclopramide and aspirin can be estimated together in human plasma and in pharmaceutical preparations by using chemical fluorescence and phosphorescence \unskip~\citep{571314:13185969,571314:13185970,571314:13185971}. 

 Most widely used methods to metoclopramide in pharmaceuticals are spectral, in which the metoclopramide is classified within the easy complexes, which can be readily estimated by the ultraviolet spectral method. The conjugation reaction can also be used to determine metoclopramide in the alkali medium. However, the best methods are used to estimate that metoclopramide hydrochloride and pyridoxine hydrochloride in human plasma are HPLC-UV methods. The electrolysis method was used to estimate metoclopramide by using a modified and electrode carbon. A sequential flow injection analysis can be performed to determine metoclopramide.\unskip~\citep{571314:13185972,571314:13185973,571314:13185974,571314:13185975}. 

 In this study, three spectral methods were used to determine metoclopramide hydrochloride using colour reagents such as diazotzil reaction with resorcinol, 8-hydroxyninol and p-benzoquinone as a coupling agent to form azo-dye in alkaline medium at room temperature \unskip~\citep{571314:13185976,571314:13185977}. 
    
\section{Materials and Methods}
\textbf{Instrumentation}

Double beam UV-visible spectrophotometer (UV-Jenawa Model 1100) was used for absorbance with a 10 mm quarty cell.

\textbf{Materials and reagents}

All reagents with a high degree of analytical purity, deionized water were also used. Metoclopramide hydrochloride was purchased from Merck. The pharmaceutical dosage used in this work Primperan tablets (metoclopramide tablets) with 10 mg of metoclopramide HCl / tablet contains 5 mg of metoclopramide (Sifar-Istanbul / Turkey) HCl / tablet and Metal Injection (Sanofi Aventis Egypt) contains 10 mg / 2 ml\unskip~\citep{571314:13185978}.


\bgroup
\fixFloatSize{images/9157e2d8-9ec9-4a2b-bca4-f5c00392afb2-upicture1.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/9157e2d8-9ec9-4a2b-bca4-f5c00392afb2-upicture1.png}{\includegraphics{images/9157e2d8-9ec9-4a2b-bca4-f5c00392afb2-upicture1.png}}{}
\makeatother 
\caption{\boldmath {Structure of metoclopramide hydrochloride}}
\label{f-d8aa01567cbb}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/37c12727-353c-46a7-9b2f-0f5e3cf030ec-upicture2.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/37c12727-353c-46a7-9b2f-0f5e3cf030ec-upicture2.png}{\includegraphics{images/37c12727-353c-46a7-9b2f-0f5e3cf030ec-upicture2.png}}{}
\makeatother 
\caption{\boldmath {Absorption spectra of metoclopramide hydrochloride azo dye with the resorcinol reagent (5.0\ensuremath{\mu }g/mL)}}
\label{f-3510a634b873}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/0c8a4511-a007-4b80-acec-21d3c11443ec-upicture3.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/0c8a4511-a007-4b80-acec-21d3c11443ec-upicture3.png}{\includegraphics{images/0c8a4511-a007-4b80-acec-21d3c11443ec-upicture3.png}}{}
\makeatother 
\caption{\boldmath {Absorption spectra of metoclopramide hydrochloride azo dye with the 8-hydroxyquinaldine reagent (10.0 \ensuremath{\mu }gmL\ensuremath{^{-1}})}}
\label{f-48c814105cf6}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/a0b468b8-3491-4e00-9965-463bdaaa0478-upicture4.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/a0b468b8-3491-4e00-9965-463bdaaa0478-upicture4.png}{\includegraphics{images/a0b468b8-3491-4e00-9965-463bdaaa0478-upicture4.png}}{}
\makeatother 
\caption{\boldmath {Absorption of metoclopramide hydrochloride with the p-benzoquinonere agent (15.0 \ensuremath{\mu }gmL\ensuremath{^{-1}})}}
\label{f-e7ce5d819d5d}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/569e3c6c-8a00-44e8-a7b2-b08ceb027ade-upicture5.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/569e3c6c-8a00-44e8-a7b2-b08ceb027ade-upicture5.png}{\includegraphics{images/569e3c6c-8a00-44e8-a7b2-b08ceb027ade-upicture5.png}}{}
\makeatother 
\caption{\boldmath {Effect of resorcinol reagent volume on absorbance }}
\label{f-64fab1d03ab1}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/04c2a3d9-70fd-4546-be31-afee715abdd3-upicture6.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/04c2a3d9-70fd-4546-be31-afee715abdd3-upicture6.png}{\includegraphics{images/04c2a3d9-70fd-4546-be31-afee715abdd3-upicture6.png}}{}
\makeatother 
\caption{\boldmath {Effect of 8-hydroxyquinalidine reagent volume on absorbance }}
\label{f-5446fd88a428}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/6d952712-2fb9-44cd-8dcc-6c251e3e0206-upicture7.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/6d952712-2fb9-44cd-8dcc-6c251e3e0206-upicture7.png}{\includegraphics{images/6d952712-2fb9-44cd-8dcc-6c251e3e0206-upicture7.png}}{}
\makeatother 
\caption{\boldmath {Effect of p-benzoquinol volume on absorbance}}
\label{f-1d1e630d403c}
\end{figure}
\egroup
\textbf{0.5\% sodium nitrite solution}

The sodium nitrite reagent was supplied by BDH Chemicals Ltd. The solution is prepared by dissolving 0.5 g of NaNO\ensuremath{_{2}} in a volumetric flask and supplemented with 100 ml of deionized water.

\textbf{Sodium hydroxide solution 0.5 N}

This solution is prepared by taking the exact weight of the base and dissolving in 100 ml of deionized water to prepare 0.5 N solution by dissolving 2 g of substance in 100 ml of deionized water \unskip~\citep{571314:13185979}.

\textbf{8-hydroxyquinaldinereagent solution 0.5\%.}

Pure reagent supplied by BDH Chemicals Ltd. This solution was prepared by dissolving 0.5 g of 8-hydroxyquinoline reagent in a 100 ml volumetric flask \unskip~\citep{571314:13185968}.

\textbf{0.5\% resorcinol}

0.5\% resorcinol solution was prepared by dissolving 0.5 g of resorcinol (supplied by BDH Chemicals Ltd) in a 100 ml flask \unskip~\citep{571314:13185981}.

\textbf{1\% p-benzoquinone solution}

1\% of the p-benzoquinone solution was prepared by dissolving 1 g in a minimum amount of ethanol and making the volume to 100 ml with ethanol \unskip~\citep{571314:13185983}.

\textbf{Sodium hydroxide solution 0.5 N}

This solution is suitably prepared by taking the exact weight of the base and dissolving it in 100 ml of deionized water to prepare a 0.5 N solution by dissolving 2 g of substance in 100 ml of distilled water \unskip~\citep{571314:13185984}.

\textbf{Hydrochloric acid solution 0,5 N}

This solution is prepared by diluting appropriately a 36\% concentrated solution of hydrochloric acid in a 250 ml graduated flask with deionized water \unskip~\citep{571314:13185985}.

\textbf{Metoclopramide hydrochloride standard solution}

Metoclopramide hydrochloride was obtained from (SDI, Samara, Iraq). A solution of 1,000 \ensuremath{\mu}g / ml metoclopramide hydrochloride was prepared by dissolved 100 mg of metoclopramide hydrochloride in 100 ml of deionized water and diluted for final concentrations \unskip~\citep{571314:13185986}.


\bgroup
\fixFloatSize{images/c4045cca-9989-4a63-a45a-43263e98ae49-upicture8.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/c4045cca-9989-4a63-a45a-43263e98ae49-upicture8.png}{\includegraphics{images/c4045cca-9989-4a63-a45a-43263e98ae49-upicture8.png}}{}
\makeatother 
\caption{\boldmath {Effect of NaNO\ensuremath{_{2}} volume on absorbance }}
\label{f-6c9dd620796a}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/164388ab-61cb-4b46-9972-61fdcbf25874-upicture9.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/164388ab-61cb-4b46-9972-61fdcbf25874-upicture9.png}{\includegraphics{images/164388ab-61cb-4b46-9972-61fdcbf25874-upicture9.png}}{}
\makeatother 
\caption{\boldmath {Effect of NaNO\ensuremath{_{2}} volume on absorbance }}
\label{f-debb3df8a6cf}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/80f3370a-4b5a-41d4-bb87-b2952de66f12-upicture10.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/80f3370a-4b5a-41d4-bb87-b2952de66f12-upicture10.png}{\includegraphics{images/80f3370a-4b5a-41d4-bb87-b2952de66f12-upicture10.png}}{}
\makeatother 
\caption{\boldmath {Effect of HCl (0.5N) volume on absorbance }}
\label{f-19ebc67fdb6e}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/e57c4c9a-19c0-4971-bc7e-6bd565cf5659-upicture11.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/e57c4c9a-19c0-4971-bc7e-6bd565cf5659-upicture11.png}{\includegraphics{images/e57c4c9a-19c0-4971-bc7e-6bd565cf5659-upicture11.png}}{}
\makeatother 
\caption{\boldmath {Effectof HCl (0.5N) volume on absorbance }}
\label{f-fc2ff9ae308b}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/b2784bab-c6e0-4c66-9041-57d61fea570a-upicture12.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/b2784bab-c6e0-4c66-9041-57d61fea570a-upicture12.png}{\includegraphics{images/b2784bab-c6e0-4c66-9041-57d61fea570a-upicture12.png}}{}
\makeatother 
\caption{\boldmath {Effect of NaOH (0.5N) volume on absorbance }}
\label{f-d330cb2a4ee0}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/409c2869-ebbd-4e1e-a296-00d5a0002b66-upicture13.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/409c2869-ebbd-4e1e-a296-00d5a0002b66-upicture13.png}{\includegraphics{images/409c2869-ebbd-4e1e-a296-00d5a0002b66-upicture13.png}}{}
\makeatother 
\caption{\boldmath {Effect of NaOH (0.5N) volume on absorbance }}
\label{f-8b6a3c45f493}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/ecc4bb41-d9e0-4997-b46e-45977090c707-upicture14.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/ecc4bb41-d9e0-4997-b46e-45977090c707-upicture14.png}{\includegraphics{images/ecc4bb41-d9e0-4997-b46e-45977090c707-upicture14.png}}{}
\makeatother 
\caption{\boldmath {The calibration curve in method-A }}
\label{f-dd9236677492}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/4c6e4d3d-ea39-474a-b420-f11ad01cf90a-upicture15.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/4c6e4d3d-ea39-474a-b420-f11ad01cf90a-upicture15.png}{\includegraphics{images/4c6e4d3d-ea39-474a-b420-f11ad01cf90a-upicture15.png}}{}
\makeatother 
\caption{\boldmath {The calibration curve in method-B}}
\label{f-9498c3451a97}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/1015f377-afa0-4839-a652-14a3859cff91-upicture16.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/1015f377-afa0-4839-a652-14a3859cff91-upicture16.png}{\includegraphics{images/1015f377-afa0-4839-a652-14a3859cff91-upicture16.png}}{}
\makeatother 
\caption{\boldmath {The calibration curve in method-C}}
\label{f-20b59ea66f03}
\end{figure}
\egroup
\textbf{Procedure}

 The three spectral methods have been used to analysis of hydrochloric metoclopramide by using different coloured reagents: 

\textbf{Method A}

Different concentrations in the range of 1-10 mg/ml (0.1 volumes, 0.3, 0.5 0.7, 0.9 and 1.0) ml of the standard solution of metoclopramide hydrochloride (100 \ensuremath{\mu}g / ml) were transferred and measured in the number of volumetric flasks with 10 ml volumes using a micro-pippet. To each flask were added 0.3 ml of 0.5\% of NaNO2 and 0.5 ml of 0.5 N of HCl. After three minutes, 0.3 ml of resorcinol was added 0.5\% and 0.5 ml of 0.5 N NaOH solution and added with deionized water. The absorbance of the coloured product was measured after 10 minutes, the colour absorbance at 415 nm against the corresponding white reagent. 

Various concentrations were prepared in the range 2.0-20 mg / ml volume (0.2.0.4,0.6,0.8,1.0,1.2,1.4,1.6.1.8 and 2.0) ml of the standard solution of metoclopramide hydrochloride (100 mg / ml) in a series of volumetric flasks (10 ml) by means of a micro-pippet. For each flask, 0.5 ml of 0.5\% NaNO\ensuremath{_{2}} solution and 0.5 ml of 0.5 N solution of 8-hydroxyquinoline and 0.5 ml of 0.5\% solution of 0.5 N NaOH and diluted to the mark with deionized water. The absorbance of the coloured product was measured at 485 nm against the solvent as blank after 10 minutes.


\bgroup
\fixFloatSize{images/f0eda2c3-9206-4cca-a08f-648a88c64e01-upicture17.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/f0eda2c3-9206-4cca-a08f-648a88c64e01-upicture17.png}{\includegraphics{images/f0eda2c3-9206-4cca-a08f-648a88c64e01-upicture17.png}}{}
\makeatother 
\caption{\boldmath {Job's method for method A}}
\label{f-7fdc44dedb99}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/f580592e-fc7b-40f7-9c5e-883c20e56c80-upicture18.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/f580592e-fc7b-40f7-9c5e-883c20e56c80-upicture18.png}{\includegraphics{images/f580592e-fc7b-40f7-9c5e-883c20e56c80-upicture18.png}}{}
\makeatother 
\caption{\boldmath {Job's method for method B}}
\label{f-fa75eff3f1d3}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/35f6b1ab-5db4-459c-b0ee-9c593163962b-upicture19.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/35f6b1ab-5db4-459c-b0ee-9c593163962b-upicture19.png}{\includegraphics{images/35f6b1ab-5db4-459c-b0ee-9c593163962b-upicture19.png}}{}
\makeatother 
\caption{\boldmath {mole ratio method for method A}}
\label{f-86ef20c162c4}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/c7195aec-14ba-414c-818d-b4120f28cbfd-upicture20.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/c7195aec-14ba-414c-818d-b4120f28cbfd-upicture20.png}{\includegraphics{images/c7195aec-14ba-414c-818d-b4120f28cbfd-upicture20.png}}{}
\makeatother 
\caption{\boldmath {mole ratio method for method B}}
\label{f-c3e8566a3c71}
\end{figure}
\egroup
\textbf{Method C}

In the series of volumetric flasks (10 ml), transfer concentrations of the standard solution of 100 \ensuremath{\mu }g / ml of metoclopramide-HCl equivalent to 1.0-30 \ensuremath{\mu }g / ml, add one ml of p-benzoquinone solution, make up the volume to 10 ml with deionized water, then the absorbance was measured after 10 minutes at 385 nm against a blank. The calibration curve was constructed from the concentrations of metoclopramide hydrochloride (\ensuremath{\mu }g / ml) against absorbance.

\textbf{The essay procedure to tablets of metoclopramide hydrochloride}


\bgroup
\fixFloatSize{images/64293079-cade-4a56-bf6c-7c1e9181119e-upicture21.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/64293079-cade-4a56-bf6c-7c1e9181119e-upicture21.png}{\includegraphics{images/64293079-cade-4a56-bf6c-7c1e9181119e-upicture21.png}}{}
\makeatother 
\caption{\boldmath {Mole ratio method for method C}}
\label{f-5603f373e04b}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/afc25d13-0531-4dcf-8d13-1eebfdcd702d-upicture22.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/afc25d13-0531-4dcf-8d13-1eebfdcd702d-upicture22.png}{\includegraphics{images/afc25d13-0531-4dcf-8d13-1eebfdcd702d-upicture22.png}}{}
\makeatother 
\caption{\boldmath {Job's method for method C}}
\label{f-5a581c200382}
\end{figure}
\egroup
10 tablets were weighed and ground well, then mixed (5 mg and 10 mg). A fraction of the powder equivalent to 0.05 g of metoclopramide hydrochloride was weighed and dissolved in deionized water, mixed well and filtered using a filter paper. Then transfer to a 100 ml flask and complete to mark with deionized water. The solution was treated in the recommended way. The working solutions were prepared by diluting the resulting solution with deionized water. 
    
\section{Results and Discussion}
\textbf{Determination of the Lambda max}

The values of the absorption spectra of the coloured complexes of the reaction between the hydrochloride salt of metoclopramide and diazonium with the resorcinol or the 8-hydroxyquinoline reagent in acidic medium (in both methods A and B respectively) with respect to the reagent target. The sample shows the maximum absorption at 415 nm (method A) and 485 nm (method B). The reaction involved two steps to give a coloured product. Initially, metoclopramide hydrochloride is treated with sodium nitrite in an acid environment to give diazonium salt. In the second phase, the diazonium ion reacts with the coupling agent of resorcinol or 8-hydroxyquinoline (method A or B) to form an orange azo dye (method) and red colour (method B) in an alkaline medium. Method C, which includes the reaction between metoclopramide hydrochloride and p-benzoquinone, shows maximum absorption at 385 nm. The absorption spectra are shown in Figures~\ref{f-3510a634b873}, \ref{f-48c814105cf6} and~\ref{f-e7ce5d819d5d}. 


\bgroup
\fixFloatSize{images/0018eb2c-3b5f-4e96-9b1e-61d6345e8421-upicture23.png}
\begin{figure*}[!htbp]
\centering \makeatletter\IfFileExists{images/0018eb2c-3b5f-4e96-9b1e-61d6345e8421-upicture23.png}{\includegraphics{images/0018eb2c-3b5f-4e96-9b1e-61d6345e8421-upicture23.png}}{}
\makeatother 
\caption{\boldmath {The proposed mechanisms of the products may be suggested as the following figures}}
\label{f-9a5bfea5c0af}
\end{figure*}
\egroup

\bgroup
\fixFloatSize{images/9eea9f2f-6cff-4ad5-8fa4-fe40c6d7aad5-upicture24.png}
\begin{figure*}[!htbp]
\centering \makeatletter\IfFileExists{images/9eea9f2f-6cff-4ad5-8fa4-fe40c6d7aad5-upicture24.png}{\includegraphics{images/9eea9f2f-6cff-4ad5-8fa4-fe40c6d7aad5-upicture24.png}}{}
\makeatother 
\caption{\boldmath {The probable reaction mechanism of the coupling reaction between metoclopramide and 8-hydroxyquinalidine (method-B)}}
\label{f-b3bc3ee0271e}
\end{figure*}
\egroup

\bgroup
\fixFloatSize{images/d3d1b920-57ed-46c9-8f22-aeacef29540d-upicture25.png}
\begin{figure*}[!htbp]
\centering \makeatletter\IfFileExists{images/d3d1b920-57ed-46c9-8f22-aeacef29540d-upicture25.png}{\includegraphics{images/d3d1b920-57ed-46c9-8f22-aeacef29540d-upicture25.png}}{}
\makeatother 
\caption{\boldmath {The probable reaction mechanism of the coupling reaction between metoclopramide and P-benzoquinone (methodC)}}
\label{f-d7a8d7170d0e}
\end{figure*}
\egroup
\textbf{Optimal conditions for the reaction}

 The effect of the various parameters on the absorption intensity, was optimized . all the experimental parameters were optimized by using 5.0, 10.0 and 15.0 mg/ml metoclopramide hydrochloride with the three methods A, B, C respectively \unskip~\citep{571314:13185987} , (Figures~\ref{f-9a5bfea5c0af}, \ref{f-b3bc3ee0271e} and~\ref{f-d7a8d7170d0e}). 

 \textbf{The effect of reagent volumes}

The reagent volumes were tested in the range of 0.1-0.5 mL and 0.5\% resorcinol. The 0.3 ml were applied in subsequent experiments (method A) because they obtained the maximum absorption and the other 8-hydroxyquinoline in the range of 0.1-0.9 ml at a concentration of 0.5\%. The 0.5 ml volume was selected as the best volume that could be used for further studies due to this volume and focuses on the maximum absorption value (method B) as shown inFigure~\ref{f-64fab1d03ab1} and Figure~\ref{f-5446fd88a428}.

The quantities were tested within 0.25-2.0 ml of p-benzoquinone at a concentration of 1\% \unskip~\citep{571314:13185988,571314:13185989,571314:13185990}. It was found that 1.0 ml was appropriate for application in subsequent experiments (method C), Figure~\ref{f-1d1e630d403c}.

 \textbf{Effect of sodium nitrite}

The different volume of 0.5\% in a range of 0.1-0.5 ml of NaNO2 was tested in the absorption density. It was observed that the volume of 0.3 ml of sodium nitrite was the optimal absorption volume (method A) (Figure~\ref{f-6c9dd620796a} ). The NaNO2 volume of 0.5 ml was also selected for density absorption (method B) (Figure~\ref{f-debb3df8a6cf}), \unskip~\citep{571314:13185991}.

\textbf{Acid effect}

Different acids such as H\ensuremath{_{2}}SO\ensuremath{_{4}}, HCl, HNO\ensuremath{_{3}} and CH\ensuremath{_{3}}COOH were tested for absorption values in methods A and B. A 0.5 N concentration of 0.5 mL of hydrochloric acid was selected as this concentration gave the highest absorption of the measured product in both methods A and B \unskip~\citep{571314:13185992} (Figure~\ref{f-19ebc67fdb6e} and Figure~\ref{f-fc2ff9ae308b} ).

\textbf{Effect of reaction time}

The azo coupling reaction was completed at 10 minutes and at 15 minutes for methods A and B. The coloured products were more stable at 24 hours in methods A and B, on the other hand, coloured products using p-benzoquinone and metoclopramide hydrochloride found completely in 10 minutes and stable for 24 hours \unskip~\citep{571314:13185993}.

\textbf{The effect of temperature}

The effect of temperature on absorption intensity was studied at different temperatures in the range 5-45\ensuremath{^{o}}C. The results indicate that the absorbance values decrease at higher temperatures, probably due to the dissociation of the compound. The maximum absorbance was found in the range of 20 to 35 \ensuremath{^\circ}C. Therefore all studies were conducted at room temperature \unskip~\citep{571314:13185994}.

\textbf{The effect of Base volume }

 The effect of base concentration on the coloured product was tested by using different basic solutions, such as ammonium hydroxide, sodium acetate, potassium hydroxide, sodium carbonate and sodium hydroxide. The product of sodium hydroxide solution was given sensitivity and stability highly, so it was used in applied in subsequent experiments. different volumes of (0.1-0.9 ml) from 0.5 M NaOH solutions were tested. The results showed that 0.5 ml of sodium hydroxide solution is sufficient to the production of maximum reproducible and absorption intensity in both methods A and B as shown in Figures~\ref{f-d330cb2a4ee0} and~\ref{f-8b6a3c45f493}. Partial decolonization of the product, maybe accruing in higher concentrations of the base \unskip~\citep{571314:13185995,571314:13185996}. 

 \textbf{The calibration curve:}

Under optimal conditions studied, the metoclopramide-HCl calibration curves were designed for all methods A, B, C, illustrated in Figures~\ref{f-dd9236677492} and~\ref{f-9498c3451a97} and Figure~\ref{f-20b59ea66f03}, the linear relationship between the concentrations of metoclopramide HCl and absorbance and 1, 0-30 \ensuremath{\mu }g / ml to methods A, B, C, respectively, with a correlation coefficient of 0.988, 0.9999 and 0.9987 respectively to methods A, B, C. It was found that the molar absorption coefficients of the methods A, B, C are 4.1224 \ensuremath{\times} 104 \ensuremath{\times} 3.0229 \ensuremath{\times} 1.7373 104 and 104 L mol-1 cm-1 for methods A, B, C, respectively\unskip~\citep{571314:13185997}. The Sandell's sensitivity was 0, 3606 \ensuremath{\times} 10 -4, 0.9834 \ensuremath{\times} 10-4 and 0.2568 \ensuremath{\times} 10-3\ensuremath{\mu }g.cm - 2 to methods A, B, C, respectively, all results are listed in Table~\ref{tw-864e55459ac8}.


\begin{table*}[!htbp]
\caption{\boldmath {The analytical parameter for methods A, B and C} }
\label{tw-864e55459ac8}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.2119\linewidth-2\tabcolsep}p{\dimexpr.2258\linewidth-2\tabcolsep}p{\dimexpr.1947\linewidth-2\tabcolsep}p{\dimexpr.36760000000000005\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Method-C & Method-B & Method-A & Parameters \\
\tblmidrule 
385 &
  485 &
  415 &
  \ensuremath{\lambda }max, nm \\
1.0-30  &
    2.0-20 &
  1.0-10 &
  Linear range \mbox{}\protect\newline (\ensuremath{\mu }g/mL) \\
1.7373x104 &
  3.0229x104 &
  4.1224x104 &
  Molar absorptivity coefficient (\ensuremath{\varepsilon }),  ( L mol-1cm-1) \\
0.2568x10-3 &
  0.9834x10-4 &
  0.3606x10-4  &
  Sandell sensitivity \mbox{}\protect\newline ( Ng cm-2) \\
0.033  &
    0.003 &
  0.018 &
  Intercept (a) \\
0.048 &
  0.085 &
  0.120 &
  Slope (b) \\
0.9979 &
  0.9999 &
  0.9988 &
  correlation coefficient (R2) \\
0.158  &
    0.553 &
  0.255 &
  LOQ(\ensuremath{\mu }g/mL) \\
0.455  &
    0.898 &
  0.512 &
  LOD(\ensuremath{\mu }g/mL) \\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Accuracy and precision of the proposed methods} }
\label{tw-1713e678b366}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.16\linewidth-2\tabcolsep}p{\dimexpr.16\linewidth-2\tabcolsep}p{\dimexpr.16\linewidth-2\tabcolsep}p{\dimexpr.1877\linewidth-2\tabcolsep}p{\dimexpr.1969\linewidth-2\tabcolsep}p{\dimexpr.1354\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\%RSD*  & \%(Recovery \ensuremath{\pm} SD)*  &  \%Relative error*  & The Amount was Found* \mbox{}\protect\newline (\ensuremath{\mu }g/mL)  & Amount was taken (\ensuremath{\mu }g/mL) & Method\\
\tblmidrule 
0.58 &
  101.50\ensuremath{\pm}0.24 &
  1.40  &
    2.03 &
  2 &
  \multicolumn{1}{p{\dimexpr(.1354\linewidth-2\tabcolsep)}}{\multirow{3}{\linewidth}{A}}\\
1.01 &
  100.80\ensuremath{\pm}0.51 &
  0.80 &
  5.04 &
  5 &
  \\
1.09 &
  101.30\ensuremath{\pm}0.33 &
  1.30 &
  10.13 &
  10 &
  \\
0.91 &
  100.80\ensuremath{\pm}0.23 &
  0.80 &
  5.04 &
  5 &
  \multicolumn{1}{p{\dimexpr(.1354\linewidth-2\tabcolsep)}}{\multirow{3}{\linewidth}{}}\\
0.89 &
  100.20\ensuremath{\pm}0.49 &
  0.20 &
  15.03  &
    15  &
  \\
0.97  &
    99.45\ensuremath{\pm}0.15  &
    0.55 &
  19.89 &
  20  &
  \\
0.83 &
  101.20\ensuremath{\pm}0.14 &
  1.20 &
  10.12 &
  10 &
  \multicolumn{1}{p{\dimexpr(.1354\linewidth-2\tabcolsep)}}{\multirow{3}{\linewidth}{C}}\\
0.96 &
  99.67\ensuremath{\pm}0.22  &
    0.33  &
    14.95 &
  15 &
  \\
0.77 &
  100.68\ensuremath{\pm}0.42 &
  0.68  &
    25.17 &
  25  &
  \\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
\textbf{Stoichiometry}

The stoichiometry of metoclopramide hydrochloride with diazonium salt and resorcinol or 8-hydroxyquinoline solutions was studied in methods A and B using the working method and the molar ratio method \unskip~\citep{571314:13185998} as shown in Figures~\ref{f-7fdc44dedb99} and~\ref{f-fa75eff3f1d3} and Figure~\ref{f-5a581c200382}. The results showed that 1: 2 was formed at 415 nm and 485 nm respectively for methods A and B, instead, the results show that a 1: 1 complex was formed at 385 nm method C using the Labor and method of molar relations (Figures~\ref{f-86ef20c162c4}, \ref{f-c3e8566a3c71} and~\ref{f-5603f373e04b}).


\begin{table*}[!htbp]
\caption{\boldmath {The application the methods for determination of metoclopramide hydrochloride in pharmaceutical preparations} }
\label{tw-84c142e66e25}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{LLLLLLLLLLL}
\tbltoprule \rowcolor{kwdboxcolor}\multicolumn{9}{p{\dimexpr(\mcWidth{1}+\mcWidth{2}+\mcWidth{3}+\mcWidth{4}+\mcWidth{5}+\mcWidth{6}+\mcWidth{7}+\mcWidth{8}+\mcWidth{9})}}{\cAlignHack Drugs brand name } & {\multirow{2}{*}{Conce. (\ensuremath{\mu }g/ml)}} & {\multirow{2}{*}{Proposed methods }}\\
\rowcolor{kwdboxcolor}\multicolumn{3}{p{\dimexpr(\mcWidth{1}+\mcWidth{2}+\mcWidth{3})}}{METOCAL INGECTION  \mbox{}\protect\newline 10mg/2ml } & \multicolumn{3}{p{\dimexpr(\mcWidth{4}+\mcWidth{5}+\mcWidth{6})}}{MECLODIN Tablets  \mbox{}\protect\newline 5mg } & \multicolumn{3}{p{\dimexpr(\mcWidth{7}+\mcWidth{8}+\mcWidth{9})}}{Metocloprmide Tablets 10mg} &  & \\
\tblmidrule 
7.0  &
    5.0  &
    3.0 &
  7.0 &
  5.0 &
  3.0 &
  7.0 &
  5.0 &
  3.0 &
  Taken conc. (\ensuremath{\mu }g/ml)  &
  \multicolumn{1}{p{\dimexpr(\mcWidth{11})}}{\multirow{4}{\linewidth}{Method A }}\\
6.89 &
  5.11 &
  3.03 &
  7.11 &
  4.99 &
  3.09 &
  7.03 &
  5.02 &
  3.05 &
  Found conc. (\ensuremath{\mu }g/ml)  &
  \\
98.42 &
  102.20 &
  101.0 &
  101.57 &
  99.80 &
  103.0 &
  100.42 &
  100.40 &
  101.66 &
  Recovery(\%) n=3  &
  \\
0.56 &
  0.99 &
  0.79 &
  1.10 &
  0.86 &
  0.97 &
  0.59 &
  0.75  &
    0.58 &
  RSD(\%),n=3  &
  \\
\multicolumn{3}{p{\dimexpr(\mcWidth{1}+\mcWidth{2}+\mcWidth{3})}}{99.73\ensuremath{\pm}0.08} &
  \multicolumn{3}{p{\dimexpr(\mcWidth{4}+\mcWidth{5}+\mcWidth{6})}}{100.05\ensuremath{\pm}0.04 } &
  \multicolumn{3}{p{\dimexpr(\mcWidth{7}+\mcWidth{8}+\mcWidth{9})}}{  101.22\ensuremath{\pm}0.02 } &
    (\%Recovery \ensuremath{\pm} SD) \mbox{}\protect\newline n=5  &
  Reference method\\
15.0 &
  10.0 &
  5.0 &
  15.0 &
  10.0 &
  5.0 &
  15.0 &
  10.0 &
  5.0 &
  Taken conc. (\ensuremath{\mu }g/ml)  &
  \multicolumn{1}{p{\dimexpr(\mcWidth{11})}}{\multirow{4}{\linewidth}{Method B }}\\
14.89 &
  10.04 &
  5.09 &
  14.77 &
  10.05 &
  5.12 &
  15.02 &
  10.12 &
  5.04 &
  Found conc. (\ensuremath{\mu }g/ml)  &
  \\
99.26 &
  100.40 &
  101.80 &
  98.46 &
  100.50 &
  102.40 &
  100.13 &
  101.20 &
  100.80 &
  Recovery (\%) n=3  &
  \\
0.98 &
  0.76 &
  0.64 &
  1.01  &
    0.89 &
  0.77 &
  0.91 &
  0.57 &
  0.66 &
  RSD(\%),n=3  &
  \\
\multicolumn{3}{p{\dimexpr(\mcWidth{1}+\mcWidth{2}+\mcWidth{3})}}{100.60\ensuremath{\pm}0.06 } &
  \multicolumn{3}{p{\dimexpr(\mcWidth{4}+\mcWidth{5}+\mcWidth{6})}}{  101.13\ensuremath{\pm}0.05 } &
  \multicolumn{3}{p{\dimexpr(\mcWidth{7}+\mcWidth{8}+\mcWidth{9})}}{  100.05\ensuremath{\pm}0.03} &
  \%Recovery \ensuremath{\pm} SD  \mbox{}\protect\newline n=5  &
  Reference method\\
15.0 &
  10.0 &
  5.0 &
  15.0 &
  10.0 &
  5.0 &
  15.0 &
  10.0 &
  5.0 &
  Taken conc. (\ensuremath{\mu }g/ml)  &
  \multicolumn{1}{p{\dimexpr(\mcWidth{11})}}{\multirow{4}{\linewidth}{Method C }}\\
14.99 &
  9.97 &
  5.11 &
  14.92 &
  9.87 &
  5.05 &
  14.89 &
  10.13 &
  5.02 &
  Found conc. (\ensuremath{\mu }g/ml)  &
  \\
99.93 &
  99.70 &
  102.2 &
  99.46 &
  98.70 &
  101.0 &
  99.26 &
  101.30 &
  100.40 &
  Recovery (\%) n=3  &
  \\
0.99 &
  1.02 &
  0.89 &
  0.72 &
  0.99 &
  0.93 &
  1.01 &
  0.82  &
    0.93  &
  RSD(\%),n=3  &
  \\
\multicolumn{3}{p{\dimexpr(\mcWidth{1}+\mcWidth{2}+\mcWidth{3})}}{100.72\ensuremath{\pm} 0.01} &
  \multicolumn{3}{p{\dimexpr(\mcWidth{4}+\mcWidth{5}+\mcWidth{6})}}{99.9 2\ensuremath{\pm} 0.05} &
  \multicolumn{3}{p{\dimexpr(\mcWidth{7}+\mcWidth{8}+\mcWidth{9})}}{101.22\ensuremath{\pm} 0.04} &
  \%Recovery \ensuremath{\pm} SD  \mbox{}\protect\newline n=5  &
  Reference method\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
\textbf{The stability constant }

The constant stability Kf of the colored products was calculated from the continuous variation data using the following equation \unskip~\citep{571314:13185999} :

$K_f=\frac{A/A_m}{(1-A/A_m)^{n+1}\;C^{n}n^{n}} $

Where: A and A\ensuremath{_{m}} are the maximum absorbance of the continuous variation curve and the absorbance corresponding to the union of the two tangents of the continuous variation curve, respectively. n is the number of reactant molecules in the reaction product, C is the molar concentration of metoclopramide hydrochloride at the maximum absorbance. K\ensuremath{_{f}} was found to be 43.6435 \ensuremath{\times} 108, 54.6261 \ensuremath{\times} 10-8 and 17.29099 \ensuremath{\times} 106 L2 mol-2 for methods A, B and C respectively. This indicates a stable reaction product. The Gibbs free energy of the reaction (\ensuremath{\Delta }G) was also calculated using the following equation \unskip~\citep{571314:13186000} :

$\triangle G=-2.303RT\log K_f $

Where R is the universal gas constant (8.314 J mol-1 deg-1). T is the absolute temperature (273 + 25 \ensuremath{^\circ} C), K\ensuremath{_{f\ }}is the reaction formation constant. It was found that \ensuremath{\Delta }G values were -43.9293 kJ / mol, -44.3735 and -51.2019 for methods A, B and C, respectively (Figures~\ref{f-9a5bfea5c0af} and~\ref{f-b3bc3ee0271e}  and Figure~\ref{f-d7a8d7170d0e}). The negative value of \ensuremath{\Delta }G refers to the spontaneity of the reaction.

\textbf{Precision and precision.}

To study the accuracy and precision of the calibration curve, solutions containing three different concentrations of metoclopramide hydrochloride were designated in methods A, B and C \unskip~\citep{571314:13186001}. The results obtained, which are summarized in Table~\ref{tw-1713e678b366} indicate a good precision and accuracy for all methods.

\textbf{Interference}

The methods developed were successfully applied to the determination of metoclopramide hydrochloride in its pharmaceutical formulation, and the results are presented in Table~\ref{tw-84c142e66e25}. The results obtained were compared statistically with the reference, the Student t-test values obtained with a 95\% level of confidence and five degrees of freedom and did not exceed the theoretical tabulated value of t = 2.77, so it does not indicate a significant difference between the compared methods. The F value (19.01) has also shown that there is no significant difference between the accuracy of the proposed methods and the reference method. The proposed methods can be used for quality control and mass analysis of metoclopramide hydrochloride, as well as in its dosage forms \unskip~\citep{571314:13186002,571314:13186003}. 

\textbf{Analytical applications }

The methods developed were successfully applied to the determination of metoclopramide hydrochloride in the pharmaceutical formulation, and the results were presented inTable~\ref{tw-84c142e66e25}. The results were statistically compared with the reference values of the Student's t-test were obtained with a confidence level 95\% and five degrees of freedom and did not exceed the theoretical tabulated value t = 2.77, so it does not indicate a significant difference between the compared methods. The F value (19.01) has also shown that there is no significant difference between the accuracy of the proposed methods and the reference method. The proposed methods can be used for quality control and routine analysis of metoclopramide hydrochloride mass and in their dosage forms\unskip~\citep{571314:13186004}.
    
\section{Conclusion}
Simple, fast and precise spectrophotometric methods have been a determination of metoclopramide hydrochloride in standard and pharmaceutical preparations. Methods A and B depended on the diazotation coupling reaction to form an azo dye with resorcinol reagent and 8-hydroxyquinoline azo dye absorbed at 415 nm and 485 nm respectively. Method C contains the reaction between the drug metoclopramide hydrochloride with p-benzoquinone to form a dye-absorbed product at 385 nm. The completion of these procedures did not require the control of temperature, solvent extraction and even its precise and sensitive methods. The proposed methods are able to determine metoclopramide hydrochloride in pharmaceutical formulations without any interference of excipients such as starch and glucose and commonly used products, suggesting easy application in the analysis of standard materials. Furthermore, these methods are extremely accurate and do not require the use of expensive instruments, which makes them suitable for routine measurement methods in laboratories.

\textbf{Expressions of gratitude}

The authors thank the professors of pharmaceutical chemistry for helping us in this manuscript.

\textbf{Contributions of the authors}

This research was conducted individually in the laboratories of the Faculty of Pharmacy, University of Basrah. This investigation was completed during a 4-month period with serious and continuous work and, therefore, excellent results were obtained by finding an easy and sensitive method to estimate metoclopramide hydrochloride.
    

\bibliographystyle{pharmascope_apa-custom}

\bibliography{\jobname}
\end{document}
