“DEVELOPMENT AND VALIDATION OF SPECTROPHOTOMETRIC METHOD FOR THE DETERMINATION OF CEFOTAXIME AND CEFTRIAXONE ”

M. PHARM DISSERTATION PROTOCOL

SUBMITTED TO THE

RAJIVGANDHIUNIVERSITY OF HEALTHSCIENCES,

KARNATAKA, BANGALORE

By,

PATIL NANDKISHOR PRAKASH,

B.Pharm,

UNDER THE GUIDANCE OF

Mr. G.M.SREENIVASA,

M.Pharm,

ASST PROFESSOR

P. G. DEPARTMENT OF QUALITY ASSURANCE

S. C. S. COLLEGE OF PHARMACY, HARAPANAHALLI-583131

2009-10

01 / Name and Address of the Candidate / PATIL NANDKISHOR PRAKASH
C/O PATIL PRAKASH DHANSINGH
AT/POST-REL
TAL-DHANGAON 425103
DIST-JALGAON
STATE-MAHARASHTRA
02 / Name of the Institution / T. M. A. E. Society’s
S. C. S. College of Pharmacy,
Harapanahalli – 583 131
(Davangere dist.) Karnataka
03 / Course of the Study
Branch / M. Pharm.,
Quality Assurance
04 / Date of Admission to course / 3rdSep.2009
05 / Title of the Topic / “DEVELOPMENT AND VALIDATION OF SPECTROPHOTOMETRIC METHOD FOR THE DETERMINATION OF CEFOTAXIME AND CEFTRIAXONE ”
06 /

Brief resume of the intended work

6.1. Need for the Study /
Enclosure – I
6.2. Review of the Literature / Enclosure – II

6.3. Objective of the Study

/ Enclosure – III
07 /

Materials and Methods

7.1. Source of data /
Enclosure – IV

7.2. Methods of collection of data

/ Enclosure – V
7.3. Does the study require any
Investigations on animals?
If yes give details / Enclosure – VI
7.4. Has ethical clearance been
obtained from your institution
In case of 7.3. / NO
08 /

List of References

/ Enclosure – VII
09 /

Signature of the candidate

/ (PATIL NANDKISHOR PRAKASH)
10.0 / REMARKS OF THE GUIDE / Above mentioned title will be carried out in our college , In the department of Quality Assurance under the guidance of G.M. SREENIVASA.
11.0 / NAME AND DESIGNATION OF GUIDE
11.1 Guideship Reference no of RGUHS
ACA/CDC/PGT-M.ph/SCS/02/2005-06/19.01.09. / Mr. G. M.SREENIVASA
Asst.Professor,
P.G.Dept.of Quality assurance,
S.C.SCollege of Pharmacy,
Harapanahalli-583131.Davanagere Dist
11.2 SIGNATURE
11.3 Co-guide
Guideship Reference No. of RGUHS
ACA-2/RP-TEA/O1/97-98/3-9-98 / Dr . E. JAYACHANDRAN
Professor & Head,
P. G. Dept. of Pharmaceutical Chemistry, S.C.SCollege of pharmacy
Harapanahalli-583131.Davanagere Dist
11.4 SIGNATURE
12 / 12.1 HEAD OF THE DEPT.
12.2 SIGNATURE / Dr. R. NAGENDRA RAO
Professor & Head,
Department of Quality Assurance,
S.C.S.College of Pharmacy,
Harapanahalli-583131
13 / 13.1 Remarks of the principal
13.2 Signature / The candidate has been permitted to carry
Out the said above mentioned title in the Dept. Of Quality assurance.
PROF. K.PRABHU
Principal
S.C.S.College of Pharmacy
Harapanahalli-583131
KARNATAKA.
Enclosure – I

6) BRIEF RESUME OF THE INTENDED WORK:

6.1 NEED FOR THE STUDY

Estimation of a given drug or medicine in the dosage forms needs the quantitative analysis of that drug or medicine in it.

Analytical methods, in a broad sense, can be classified into chemical methods and instrumental methods. Chemical methods are defined as those that depend on chemical operations in combination with the manipulation of simple instruments. In general, the measurement of mass, i.e. gravimetric and of volume, i.e., volumetric analysis falls in this class. An instrumental method encompasses the use of more complicated instrumentation based on analytical methods1.

Validation of analytical methods and equipment are required by many regulations, regulatory guidance documents, quality standards,and company policies for establishment of sensitive and accurate method for the estimation of compound. If executed correctly, they also help to improvethe reliability, consistency and accuracy of analytical data1. To review several aspects of the validation of qualitative methods of analysis, to revise performance parameters Accuracy,Precision,Linearity,Range,Lower limit of detection &Quantitation and to define more appropriate ones when necessary. This is done to establish process capability and to confirm product acceptability2-6.

Methods for estimation of compounds by UV-Vis-Spectroscopy are7-18:

  1. Assay as a single-component sample
  2. Simultaneous equation method
  3. Geometric correction method
  4. Orthogonal polynomial method
  5. Difference spectrophotometry
  6. Derivative spectrophotometry
  7. Least square approximation
  8. Colorimetric method
  9. Redox reaction followed by complex formation

Antimicrobial drug are the greatest contribution of the 20thcentury to therapeutics . Their advent changed the outlook of the physician about the power drugs can have on diseases. They are one of the few curative drugs. Their importance is magnified in the developing countries, where the infective diseases are predominant. Cephalosporin’s are Beta-lactum19 semi-synthetic antibiotics play important role in the antimicrobial activity .

Cefotaxime is a third generation intravenous cephalosporin antibiotic. It has broad spectrum activity against Gram positive and Gram negative bacteria. It does not have activity against Pseudomonas aeruginosa. Cefotaxime works by inhibiting bacterial cell wall biosynthesis. A positive feature of cefotaxime is that it display a resistance to penicillinases and is useful to treat infections that are resistant to penicillin derivatives.

Used to treat gonorrhoea, meningitis, and severe infections including infections of the kidney (pyelonephritis) and urinary system19. Also used before an operation to prevent infection after surgery. Cefotaxime sodium is marketed under various trade names including Claforan (Sanofi-Aventis).

CEFOTAXIME

(6R,7R,Z)-3-(acetoxymethyl)-7-(2-(2-aminothiazol-4-yl)-2-(methoxyiminoacetamido)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid20.

Ceftriaxone is a cephalosporin/cephamycin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. Ceftriaxone has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of Ceftriaxone results from the inhibition of cell wall synthesis19 and is mediated through Ceftriaxone binding to penicillin binding proteins (PBPs). Ceftriaxone is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases

For the treatment of the infections (respiratory, skin, soft tissue, UTI, ENT) caused by S. pneumoniae, H. influenzae, staphylococci, S. pyogenes (group A beta-hemolytic streptococci), E. coli, P. mirabilis, Klebsiella sp, coagulase-negative staph19.A broad-spectrum cephalosporin antibiotic with a very long half-life and high penetrability to meanings, eyes and inner ears. It’s show solubility in water .

CEFTRIAXONE

(6R,7R)-7-{[(2Z)-2-(2-amino-1,3-thiazol-4-yl)->2-(methoxyimino)acetyl]amino}-3-{[(2-methyl-5,6-dioxo-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl)thio]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid20.

Enclosure – II

6.2 REVIEW OF LITERATURE:

The review of various published work related to subject and objectives of the study has revealed the following:

.Lakshmi K.S., Ilango K., Nithya Mathi N., Balaji S., KibeVictor D.W. and Sathish Kumar V. Spectrophotometric Methods for the Estimation of Ceftriaxone Sodium in Vials. Lakshmi K.S. et al, Int J Pharm Sci, Vol 1 (1) 2009, 22-25.

Mruthyunjayaswamy B.H.M , Hiremath Basavaraj ,S . Appala raju , New Spectrophotometric methods for the determination of cefotaxime sodium in pure and in pharmaceutical dosage foams . Int J Pharm Sci, Vol 4 (4) 2006, 997.

Mruthyunjayaswamy B.H.M , Hiremath Basavaraj ,S . Appala raju , New Spectrophotometric methods for the determination of ceftriaxone sodium in pure and in pharmaceutical dosage foams . Int J Pharm Sci, Vol 4 (4) 2006, 791.

Ibrahim A. Darwish, Kinetic spectrophotometric methods for determination of trimetazidine dihydrochloride, Analytical Chimica Acta 551 (2005) 222–231.

Mahmoud A. Omar, Osama H. Abdelmageed, and Tamer Z. AttiaKinetic Spectrophotometric Determination and validation of Certain Cephalosporins in Pharmaceutical Formulations Int J Anal Chem. 2009; 2009: 596379.

Manikya Sastry T, Trilochan Padhi and Ramakrishna K, Development and Validation of Spectrophotometric method for the Determination of Abacavir sulphate in bulk and formulations.IJCS vol-7(2):2009,1045.

 Emirhan Nemutlu / Sedef Kır, Validated Determination of Meloxicam in Tablets by Using UV Spectrophotometry, Hacettepe University, Journal of Faculty of Pharmacy Volume 24 / Number 1 / January 2004 / 13-24.

Shalinia. S, Shanoojaa.V.P, Abdul Jameela S, Basima , Harilala.K.K, Harish Rajakb, Ravichandrana.V, Apllication of U V-Vis-Spectroscopic method for estimation of Lamivudine in tablets, Digest Journal of Nanomaterials and Biostructures Vol. 4, No.2, June 2009, p. 357 – 360.

Gurupadayya.B.M , Vijaya.B.V, Prasad.R.D.V and Hemlatha.S, Spectrophotometri method for the estimation of Amrinone Lacted in bulk & pharmaceutical formulation .Indian drugs vol -45 ,No-3 ,March 2008,p-193.

Srinivasan.K.K, Shiwaikar.A, Joseph.A, Jacob and Prubu.L.S, Simultaneous estimation for the analysis of Salbutamol Sulphate and Ambroxole Hydrochloride in a solid dosage forms by U.V.Spectroscopy.Indian drugs Vol-42,No-9,Sep-2005,p-576.

Enclosure – III

6.3) MAIN OBJECTIVE OF THE STUDY

The present work is in an attempt to:

  1. To develop selective, precise and sensitive method for the development and estimation of the cefotaxime and ceftriaxone.
  2. The analytical method so far developed is to be validated.
  3. The work involves use of analytical techniques such as Spectroscopy.
  4. The method appears to be suitable for the quality control in pharmaceutical industry.

Enclosure – IV

7. MATERIALS AND METHODS

7.1) SOURCE OF DATA.

The preliminary data required for the experimental study was obtained form

  1. Indian Pharmacopoeia 1996
  2. Chemical sources
  3. Scientific sources
  4. Journals
  5. Internet sources
  6. Relevant books
  7. S.C.SCollege of Pharmacy (Library)
  8. CD-ROM Search

Enclosure – V

7.2) METHODS OF COLLECTION OF DATA

Data pertaining for the present study will be obtained from Quality Assurance Laboratory of S.C.S College of Pharmacy, Chemical abstracts, Scientific abstracts, Journals and Internet sources etc..,

The experimental and spectral data pertaining for the present study is obtained from the various techniques adopted in the estimation of cefotaxime & ceftriaxone, in pharmaceutical preparation. The Spectrophotometric method shall be developed and validated in Q.A. lab of S.C.S.College of pharmacy.

Enclosure – VI

7.3) Does the study require any investigation to be conducted on patients/ Humans/ Animals? If so describe briefly

Not Applicable

7.4) Has ethical clearance been obtained from your institution in case of 7.3?

Not Applicable

.

Enclosure – VII

8. REFERENCES:

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    Using UV Spectrophotometry, Hacettepe University, Journal of Faculty of
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  1. Greici Cristiani GOMES & Hérida Regina Nunes SALGADO, Validation of UV
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