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\begin{document}


\def\RunningAuthor{Vennkata Ramana Pindi B et al.}
\firstPage{740}
\articleType{Original Article}
\receivedDate{16 Nov 2020}
\acceptedDate{19 Dec 2020}
\revisedDate{18 Dec 2020}
\journalVolume{2020, 11 (SPL4)}
\journalDoi{ijrps.v11iSPL4.4057}
\copyrightYear{2020}
\def\authorCount{4}
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\def\journalTitle{International Journal of Research in Pharmaceutical Sciences}

\title{Evaluation and authentication for metformin HCL, Glimepride, atorvastatine by using bulk HPLC pharmaceutical dosage form}
\author{Vennkata~Ramana~Pindi~B\textsuperscript{*}\textsuperscript{1},  
            Sravani~G\textsuperscript{2},  
            Ardhanaari~M\textsuperscript{3}, 
            Karthigai~Priya~M\textsuperscript{3}~\\[5pt]{\textsuperscript{1}Department of Surgery, Konaseema Institute of Medical Sciences Research Foundation, Amalapuram, Andhra Pradesh, India}~\\{\textsuperscript{2}Department of OBG, Konaseema Institute of Medical Sciences Research Foundation, Amalapuram, Andhra Pradesh, India}~\\{\textsuperscript{3}Department of Psychiatry, Meenakshi Academy of Higher Education and Research, Chennai, Tamilnadu, India}}

\begin{abstract}
Reverse phase chromatographic techniques are used for analyzing drugs. It is advanced analytical instrumentation method used for analysis of drugs. A novel accurate, precise, simple, \& selective RP- HPLC technique is established and authorized for stability representing RP {\textendash} HPLC technique for simultaneous assessment of Metformin HCL, Glimepiride \& Atorvastatin in bulk \& pharmaceutical dosage form by RP{\textendash} HPLC technique. The technique on Luna C 18, 250mm \ensuremath{\times} 4.6 mm, 15 \ensuremath{\mu}m. Column with a mobile phase comprising of buffer and acetonitrile in ratio of (85:15 v/v) and 1.0ml/ minflow rate. The detection is 258 nm. The retention time for metformin HCL, Atorvastatin \& Glimepiride are discovered to be 3.266, 5.237 and 8.457 correspondingly. The technique authorized accordingly to ICH rules for precision, specificity, LOQ, LOD, accuracy, robustness, \& linearity. The technique demonstrates best recovery \&reproducibility with \% RSD lower than 2. The suggested technique is discovered to be precise, simple, accurate, specific, \&linear. The results are within the acceptance limits of lower than 2\% signified that suggested technique has best reproducibility. The toughness of developed technique is validated by altering mobile phase composition, flow rate, and changing wavelength. The \% RSD was found within the limits i.e., should not be more than 2.0. 
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Rp- Hplc,\newline Metformin (MET),\newline Glimepiride (GLP),\newline Atorvastatine,\newline pioglitazone hydrochloride (PIO),\newline mobile phase (MP),\newline nylon membrane filter (NMF),\newline volumetricflask (VF),\newline standard deviation (SD)
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ Vennkata~Ramana~Pindi~B~\\ Phone:\ 9866955920~\\  Email:\ Ramanapindi@gmail.com
        \par}\vspace*{-11pt}\hrulefill\par{\fontsize{12}{14}\selectfont ISSN: 0975-7538}\par% 
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\section{Introduction}
A quick, precise, simple, liquid chromatography technique is established for concurrent assessment of GLP, MET, \& PIO exist in multicomponent dosage forms \unskip~\citep{972566:21125625}. The chromatography is completed isocritically at 25\text{\textordmasculine}C \ensuremath{\pm} 0.5 \text{\textordmasculine}C on an ``Inertsil-ODS-3 (C-18) Column (250\ensuremath{\times} 4.60 mm, 5 \ensuremath{\mu}m)'' with MP collected of methanol-phosphate support (pH 4.3) in 75: 25 v/v ratio at 1 ml/minflow rate. Discovery is done utilizing an UV-PDA identifier at 258 nm \unskip~\citep{972566:21125627}. Factors like accuracy, specificity, linearity, recovery, precision, \& ruggedness have been surveyed as stated in ``International Conference on Harmonization rules''. The maintenance times for PIO, MET, \& GLP are7.12 + 0.5, 2.66 + 0.5, \& 10.17 + 0.5 min, correspondingly \unskip~\citep{972566:21125634}. The linearity \% \& range recoveries for PIO, MET, \& GLP have been 10-150, 10-5000, and 1-10 \ensuremath{\mu}g/Ml \&100.06\%, 100.4\%, and 100.2 \% correspondingly \unskip~\citep{972566:21125642}.  
    
\section{Materials and Methods}
\textbf{Chemicals}

HPLC grade Acetonitrile, HPLC grade Water, are used as solvents. Ortho phosphoric acid of Analytical grade was used in the buffer preparation \unskip~\citep{972566:21125638}.

\textbf{Drug Samples}

Metformin Hcl, Glimepiride, and Atorvastatin.

\textbf{Materials}

The ``correlation coefficients'' for whole segments are near 1. The overall SDs for 3 repeat estimations in 3samples concentrations in tablets are in every case under 2 \% \unskip~\citep{972566:21125640}Table~\ref{tw-46514a199fab}.


\begin{table}[!htbp]
\caption{\boldmath {Table showing the specification of instrument} }
\label{tw-46514a199fab}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.32239999999999995\linewidth-2\tabcolsep}p{\dimexpr.6776\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Instrument & Specifications\\
\tblmidrule 
HPLC &
  Water, 2695 separation module\\
Software &
  Empower, version 2.0\\
Detector &
  UV- Visible detector\\
Analytical balance &
  Shimadzu\\
\tblbottomrule 
\end{tabulary}\par 
\end{table}
\textbf{Method Development}

The present investigation was designed to establish easy and sensitive RP- HPLC technique for quantitative assessment of Metformin Hcl, Glimepiride and Atorvastatin in bulk drug \& Pharmaceutical dosage forms. Trails performed for HPLC technique expansion of Metformin Hcl, Glimepiride, and Atorvastatin \unskip~\citep{972566:21125629}. 

\textbf{Selection of Wave Length (For Detection)}

The choice of detection wave length was based on the scanned absorption for Metformin Hcl, Glimepiride, and Atorvastatin. 

The UV- Spectrum of Metformin Hcl, Glimepiride and Atorvastatin was obtained separately by scanning the sample over the wave length range 200-400nm against blank as methanol. 

After thorough analysis of spectra, the wavelength 253 nm is designated for next examination \unskip~\citep{972566:21125636}.

\textbf{Optimized Method}

\textbf{Buffer Solution Preparation}

Mix 1ml of ortho phosphoric acid in 1 litre water, filtered through 0.45\ensuremath{\mu}m NMF \unskip~\citep{972566:21125624}.

\textbf{Mobile Phase}

The acetonitrile combination and 0.1\% ``ortho phosphoric acid'' in ratio of 15: 85 \% v/v was sonicated to degas and filtered through 0.45\ensuremath{\mu}m NMF \unskip~\citep{972566:21125641}.

\textbf{Preparation of Diluent}

Acetonitrile: Buffer (15: 85 v/v).

\textbf{Chromatographic Conditions}

Column : Zodiac C18 (250 \ensuremath{\times} 4.6 mm, 5\ensuremath{\mu})

Mobile Phase : Buffer: Acetonitrile (85: 15v/v)

Flowrate : 1.0 ml / min 

Detection wavelength : 258 nm Injection volume : 10\ensuremath{\mu}l

Temperature : Room temperature

Runtime : 20 min Retention time for Metformin HCL is about 3.066 Retention time for Atorvastatin is about 5.237 Retention time for Glimepiride is about 8.457.

\textbf{Observation}

The method is suitable for validation.

\textbf{Preparation of Standard Stock Solution}

\textbf{Solution A: Atorvastatin}

Accurately 10.1 mg of Atorvastatin was weighed and transferred into 100ml VF that is considered as working standard solution. Add 80 ml of ``diluent sonicate'' to dilute \&dissolve to volume with diluents \unskip~\citep{972566:21125631}.

\textbf{Solution B: Metformin}

To prepare working standard solution of metformin 50.9 mg is weighed accurately and transferred into 100mlVF. Include 80ml of ``diluent sonicate'' to dilute \& dissolve volume with diluents \unskip~\citep{972566:21125635}.

\textbf{Solution C: Glimepiride}

The weigh precisely 10.2 mg of Glimepiride working standard into 100ml VF. Include80 ml of``diluent sonicate'' to dilute \& dissolve to volume with diluents.

Moreover, dilute 1ml of aforementioned solution to 10 ml with diluents. Moreover, dilute every 1 ml of solution- A, B \&C to 100 ml with diluent \unskip~\citep{972566:21125637}.

\textbf{Sample Solution Preparation}

The weigh precisely about 82.49mg of sample into 100 ml VF. Include 80 ml of diluent sonicate to dissolve \& dilute to volume with diluent. Further dilute 5 ml of above solution to 50 ml with diluent \unskip~\citep{972566:21125639}.

\textbf{Procedure}

Inject 5 \ensuremath{\mu}l of standard preparation 5 times \& sample preparation in Chromatograph. Notice the Chromatograms \&calculate peak responses of Metformin Hcl, Atorvastatin and Glimepiride. The framework appropriateness factors must be met. From peak responses, estimate content of Metformin Hcl, Atorvastatin and Glimepiride in the sample \unskip~\citep{972566:21125630}.

\textbf{Method Validations Linearity}

Linearity of detector responses for metformin, glimepiride and atorvastatin was established. 6 concentrations extent from 0 \ensuremath{\mu}g/ mL to 14 \ensuremath{\mu}g/ml,1\ensuremath{\mu}g/ml to 28\ensuremath{\mu}g/ml, and 1\ensuremath{\mu}g/ml to 17\ensuremath{\mu}g/ml of target concentration were organized Graph~\ref{f-81a95f9f4ede}. The last concentration of every solution in \ensuremath{\mu}g/ml is estimated and plotted against response of area. The y-intercept, slope, \&correlation coefficient (R) are estimated \unskip~\citep{972566:21125628}.


\bgroup
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\centering \makeatletter\IfFileExists{images/f52982ed-7cfe-4630-bff4-17ac6ac00daf-upicture1.png}{\includegraphics{images/f52982ed-7cfe-4630-bff4-17ac6ac00daf-upicture1.png}}{}
\makeatother 
\caption{\boldmath {Graph representing Linearity of results obtained}}
\label{f-81a95f9f4ede}
\end{graph}
\egroup
\textbf{Accuracy}

A study of accuracy was conducted for Metformin Hcl, Glimepiride and Atorvastatin in triplicate (50\%, 100\%, and 150\%) according to test technique with similar number of drug comprising into every volumetric flask for every spike level to obtain concentration of Glimepiride, Metformin, and Atorvastatin equal to 50\%, 100\% \& 150\% of labelled amount \unskip~\citep{972566:21125626}Graph~\ref{f-9ba2eab1e1c0}.


\bgroup
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\centering \makeatletter\IfFileExists{images/2bc95df9-cf54-4de0-92fc-85f606c5928a-upicture2.png}{\includegraphics{images/2bc95df9-cf54-4de0-92fc-85f606c5928a-upicture2.png}}{}
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\caption{\boldmath {Graph showing accuracy obtained for drugs}}
\label{f-9ba2eab1e1c0}
\end{graph}
\egroup
\textbf{Robustness}

The suggested technique robustness is described by aliquots examination from homogenous lots by diverse physical factors such as mobile phase, flow rate, composition, wavelength that might fluctuate but responses are within identified bounds of assay \unskip~\citep{972566:21125632}.

\textbf{LOD and LOQ}

The LOQ \&LOD are estimated by technique relied on SD (\ensuremath{\sigma  }) \& CC slope, utilizing the below equation.
\begin{eqnarray*}\style{font-family:'Times New Roman'}{\style{font-size:8px}{LOD\;=\;3.3\;\sigma /S;\;LOQ\;=\;10\sigma /S}} \end{eqnarray*}
Here,

\ensuremath{\sigma  } be SD response 

s = CC slope 

Table~\ref{tw-27f8796ee7b0}  showing results obtained for LOD and LOQ values.


\begin{table}[!htbp]
\caption{\boldmath {Table showing LOQ \& LOD Values} }
\label{tw-27f8796ee7b0}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.4176\linewidth-2\tabcolsep}p{\dimexpr.29179999999999996\linewidth-2\tabcolsep}p{\dimexpr.2906\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Sample & LOD & LOQ\\
\tblmidrule 
Metformin Hcl  &
  10.1  &
  10.1 \\
Atorvastatin  &
  50.2  &
  50.2 \\
Glimepiride  &
  10.2  &
  10.1 \\
\tblbottomrule 
\end{tabulary}\par 
\end{table}
\textbf{Solution stability (SS)}

The SS of Metformin, Glimepiride, \& Atorvastatin diluents ware described by storing sample solutions in tightly capped VF at 24 hrs room temperature. The quantity of Metformin Hcl, Glimepiride, and Atorvastatin are estimated at diverse time intervals at 6, 12, 18, and 24 hrs and results attained are compared with freshly prepared solutions of Metformin Hcl, Glimepiride, and Atorvastatin \unskip~\citep{972566:21125633}.

\textbf{Forced degradation studies}

The technique specificity is established through forced degradation surveys performed on sample utilizing oxidative, acid, thermal, reductive, photolytic, alkaline, \&degradations. The sample is uncovered to these situations \& significant peak is surveyed for peak purity, therefore representing that technique efficiently detached degradation products from pure active ingredient \unskip~\citep{972566:21125643}. The monitoring guidance in ``ICH Q2A, Q2B, Q3B, and FDA 21 CFR section 211'' needs validation \& improvement of stability representing potency assays.
    
\section{DISCUSSION}
In HPLC technique, the circumstances are optimized to attain tolerable division of eluted compounds. Primarily, diverse MP compositions are tried to distinct compounds. The flow rate \&MP assortment is relied on peak factors, resolution, run time. The framework with buffer acetonitrile (85:15 v/v) with 1.0 mL/ min flow rate is quite strong. The optimum wave length for detection is 258 nm at best detector response for all the drugs is attained. The retention times for Metformin Hcl, Glimepiride, and Atorvastatin is discovered to be 3.066, 8.457 \& 5.237 min respectively. The linearity of Atorvastatin, Glimepiride and Metformin Hcl was carried out at different concentrations ranging from 0-3.03 \ensuremath{\mu}g/mL and 0 {\textendash} 150.60\ensuremath{\mu}g/ml. Correlation coefficient was found to be 0.9999, 0.99967, and 0.99964 which indicates that the concentration had given good linearity. The \% RSD values of Atorvastatin, Glimepiride and Metformin Hclfor precision of system \& technique is discovered to be 0.225, 1.527, 0.261 and 0.283, 0.765, 0.669 respectively. 
    
\section{Conclusion}
The present investigation led to the development of new analytical technique for assessment of potent drugs Atorvastatin, Metformin Hcl \& Glimepiride. All the methods developed provide a wide choice for routine determination of Atorvastatin, ``Glimepiride \& Metformin Hcl'' in bulk and pharmaceutical dosage forms.

\textbf{Funding Support}

The authors declare that there is no funding support for this research work.

\textbf{Conflict of Interest}

The authors declare that there is no conflict of interest among the authors and research.
    

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