TABLE OF CONTENTS
CHAPTER ONE
1.0
INTRODUCTION
1.1
HISTORY OF TRAMADOL AND ITS STASTITICS
CHAPTER TWO
20
CHEMISTRY OF TRAMADOL AND
CLASSIFICATION OF TRAMADOL
2.1.1 STRUCTURE
AND CHEMICAL NAME OF TRAMADOL CHEMICAL STRUCTURE OF TRAMADOL
(cis-configuration)
2.1.2 SYNTHESIS
OF TRAMADOL MECHALISM OF ACTION
2.1.3 CHEMICAL
AND PHYSICAL PROPERTIES OF TRAMADOL
CHAPTER
3
3.0 USES
OF TRAMADOL
3.0 THERAPEUTIC
APPLICATION AND EXTENT OF THERAPEUTIC USES AND EPIDMIOLOGY
3.1.0 EFFECT
OF TRAMADOL (POSITIVE)
3.1.1 ADVERSE
REACTIONS IN HUMANS
3.12
HARMFULL USE OF TRAMADOL
3.1.3 ABUSE
OF TRAMADOL AND DEPENDENSE
3.1.4 TOXICOLOGY
OF TRAMADOL
3.1.5 CONTROL
OF TRAMADOL AND IMPACT OF SCHEDULING
4.0
SUMMARY
REFERENCES
CHAPTER ONE
1.0
INTRODUCTION
Tramadol
hydrochloride [TMH], chemically known as
[1R,2R]-vel-2-[dimethlamino]-1-[3-methoxyphecy] cynonexanol [figure]is a synthetic
analogue of codine and is a naturally acting analgestic agent.
1. 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
2. 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.
3. TMH
is official in European pharamacopeia [EP]
4. It
describe nonaqueoua titration with perchloric acid as tritrant the end point
being located pontentiometically ultraviolet spetrophometry.
High
performance liquid 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 qualification 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 pharmaceutical 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 detection for the determine nations of TMH in different
matrices. A sensitive UPLC-MS\MS method for TMH in urine and whole blood in forenoons
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.
TABLE 1: LINEARITY AND
REGRESSION PARAMETERS WITH PRESSISION DATA
Parameters
|
Value
|
Linear range ng ml-1
|
0.5-300
|
Limits of quantification [LOG], ng ml-1
|
0.2
|
Slope [b]
|
|
Intercept [a]
|
19330.0
|
Correlation coefficient [r]
|
0.9999
|
Standard deviation of b,[sb]
|
76.0
|
Standard deviation of a [sa]
|
13694.5
|
By
liquid chromatography positive etectrospray ionization tender mass spectrunetry
has recently been used for the multiresidue analysis of drugs of abuse in waste water and surface
water.
Though
a member of liquid chromate graphing
method have earlier propose for TMH no attempt has been made to apply these new
type of LC [UPLC] for pharmaceutical except in body fluids oral fluids and
surface and waste water despite its many fold advantages.
The
aim of this work was to develop a rapid, precise, accurate and validated
stability indication UPLC method for the
determination of tramadol HCL in bulk and tablet. This was accomplish with a
water acquity UPLC system and acquity UPLC system and acquity BEH column
[C18,100mm 21MM,AND 1.7 JUM]. The stability indicating power of the method was
established by comparing the
chromatogram obtained under optimize condition before forced degredation with
those after degredation via acidic, basic, hydrytitic, oxidative then and
photolytic stress condition.
1.1 HISTORY OF TRAMADOL AND ITS STASTITICS
Tramadol
[brand name ultra] is an oral, opiod pain relieving drug that is marketed under
a veriety of trade names with ultram and ultracent being the most widely
prescribe and recognized.
Tramadol
is most often prescribe to that moderate level of pain including dental,
osteoporosis, and neuropathy in both acute and chronic setting it is also
improved for treating cancer pain in period lees than three months.
Tramadol
is thought to be safe due to lower risk of tolerance abuse, and dependence, but
it has lower clinical value then other opiates. The drugs has only about
one-tenth of the pain-reducing qualities of morphine.
Tramadol
stand apart from other operates for two reasons;
· Tramadol
is a fully synthetic drug, which means that it is man-made and does not occur
in nature. This is in contract to morphine and codine-which are natural operates
derived from the opium poppy. It also differs from drugs like hydromorphine, hydro
codeine, and oxycodone which, whole also semi synthetic and made in a
laboratory, still retain some natural qualities.
· Tramadol
has an uncommon, anal- acting benefit. Tramadol works as an opiate in the
expected way to manage the perception of pain, but be young that, it allows
increase availability of two other neuro transmitter chemical in the brain
called norepinephrine and Serotonin-Norepinephrine is note for its ability to
improve concentration, and serotonin manges an array of function including
sleep and mood.
Comepared to others drugs and medications,
tramadol is relatively young. The drugs was created by a German drugs and
company that specialize in treating pain in 1962. The medication was tested for
15 years in 1977 under the name tramal. The drugs was a success for the company
tramadol is widely prescribe around the world for pain relief .however it was
not until 1995 that the drugs become available in the US. Now, the medication
is quite popular in America.
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