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Chapter One

1.0 Introduction

Tramadol hydrochloride [TMH],chemically known as [1R,2R]-vel-2-[dimethlamino]-1-[3-methoxyphecy] cynonexanol[figure]is asynthetic analogue of codine and is a antrally acting analgestic agent.

It is metabolized by the anytochrom P450 enzyme system in the liver to form eleven matabolites of which 0-desmethy tramado [M1] predomilate and has anagestic properties

It has been used since 1977 for the relief of severe physical pain and has been the most widely sold opioid analgestic drug in the world.

TMH is official in European pharamacopeia [EP]

It describe nonaqueoua titration with perchloric acid as tritrant the end point being located pontentiometically ultraviolet spetrophometry.

High perfomance liguid chometrography, thin layer chomatrography –detromrtry capillary isotachophysis flow injection chemileum nescence spectrometry, voitametry ion-setective-bised potentionmetry visible spectrometry, and trtrimetry for determining TMH in pharmaceutical dosage forms.

In addition, there have been part of its assay when present in combination with other drugs. TDH and ibuprofen ware assayed simultaneously by the first –order denvative spetrophytometry and HPLC with UV-detected. The TMH along with detetroprofen and haloperidot have been determine by HPLC-deode array detection [DAD] method simultaneous analysis of TMH and acceclofenac in a commercial tablet was accomplished also by HPLC with UV-detection method. Simultaneous determination of paracetamol, TNH and dompenriodone in combine dosage form using RP-HPLC has been reported by karun akaran etal.

In recent years, there has been an increased tending towards development of stability –indication analysis, using the approach to stress testing enshrimed in international conference harmonization [ICT] guideline Q2A[R2].this approach is being extended to pharmaceutical to enable accurate and prease gualification of drugs in the presence of their degradation products. Though there are many reported methods of the analysis of TMH either alone or in combination with other drugs in pharmaceutical dosage forms, the literate on the stability –indication method is scarce. Mohammed etal have elevated the stability of tramadol enantiomers using a chiral stability – indicating capillary electrophoresis method and its application to pharamaceutical analysis. Chemical stability of TMH in infection has been reported by Gupta.

Ultra performance liquid chromatography [UPEC] is a relatively new technique giving new possibility in liquid chromatography especially concerning stecrise of time and anal solvent consumption. UPLC system is designed in a special way to withstand high system back pressure special analysis colume UPLC acquity UPLC BEH C18 packed with 1.7 jum partickes are used in the system. The UPLC system allows shortening analysis time up to nine time compared to used convention of HPLC system, but separation efficiency remains the same or even improve as efficiency and speed of analysis are of great importance in many application of liquid chonmatography, especially in pharmaceutical, toxicological and chemical analysis, where cost, UPLC could play significant role in the future of liquid chromatography.

Three report are found in the literature dealing with the application of UPLC with mass spectrometric dectection for the determine nations of TMH in different matrices. A sensitive UPLC-MS\MS method for TMH in urine and whole blood in forensosn context has very recently been reported kasprzk-hordarn etal. Determine TMH in surface water by solid-phase extraction and UPLC-positive etectrospray ionization mass spectrometry.

Simultaneous screening and quantification of 29 drugs abuse including TMH in oral third has seen reported by badawi atai sohd phrase extraction and UPLC-MS/MS.

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