6
6.6.
7
/
Brief resume of the intended work:
6.1 Need for the study:Multi-ingredients formulations are useful in management of various ailments where in, the intake of large number of dosage is avoided. Triamterene is a directly acting potassium–sparing diuretic. It is a pteridine derivative. It blocks the reabsorption of sodium ion and blocks the secretion of potassium ions. Triamterene shows hyperkaelemia as its major side effect. Inorder to overcome this effect, it is used in combination with a thiazide diuretic which counteracts the side effect of triamterene by its hypokaelemic effect.1 It is official in Indian Pharmacopoeia 1996.2
Benzthiazide is a thiazide like diuretic, it’s primary site of action is on distal tubule of nephron where it acts by inhibiting sodium chloride symport at luminal membrane.3
Combination of Triamterene and Benzthiazide are used in treatment of edema
and hypertension.4
In the literature survey it was found that Triamterene and Benzthiazide are estimated independently and in combination with other drugs by several Bioanalytical, HPLC and Spectrometric methods. But no method found for simultaneous estimation of Trimaterene and Benthiazide even though this multi- ingredient’s formulation is available in market. In the view of the need in the industry for routine analysis of Triamterene and Benzthiazide in formulation, attempts are being made to develop simple and accurate analytical methods for simultaneous estimation of Triamterene and Benzthiazide and extend it for their determination in formulation.
Analytical monitoring of a pharmaceutical product or specific ingredients within the product is necessary to ensure its safety, efficacy throughout all phases of its shelf life.
Analytical validation is the corner stone of process validation. Without proven measurement system it is impossible to confirm whether the manufacturing process has done the purpose what it is expected to do. Hence there is a need to validate the new methods developed.
6.2. Drug profile :
Triamterene 1,2 :
IUPAC name : 2,4,7 – triamino-6-phenylpteridine
Molecular formula : C12H11N7
Molecular weight : 253.27
Category: Diuretic.
Description: Yellow crystalline powder, odourless.
Solubility : Soluble in methanol. Very slightly in water, in chloroform and
ethanol(95%)
Benzthiazide 3,4 :
IUPAC name : 3-[(benzylthio)methyl]-6-chloro-4H-1,2,4-benzothiadiazine-7-
sulfonamide 1,1-dioxide.
Molecular formula: C15H14ClN3O4S3.
Molecular weight: 431.94.
Category: Diuretic, antihypertensive.
Description: Crystalline powder, bitter taste.
Solubility: Soluble in methanol, alkaline solutions. Practically insoluble in water.
6.3 Review of literature :
· Falco CP, Hernandez RH, Cabeza AS.5 Determination of Triamterene in urine by HPLC using fluorescence detection and column-switching.
· Yap B, Kazlauskas R.6 Rapid HPLC screening of Chlorthiazide, Torasemide,Xipamide and Benzthiazide in Sydney 2000 olympic games.
· Maslanka A, Krzek J, Stolarczyk.7 Simultaneous estimation of Hydrochlorthiazide, Triamterene, Furosemide and Spiranolactone by densitometric TLC.
· Stolarczyl M, Apola A, Krzek J, Lech K.8 Simultaneous estimation of Triamterene and Hydrochlorthiazide in tablets using derivative Spectroscopy.
· Kargosha K, Sarrafi HM.9 Spectrophotometric simultaneous estimation of Triamterene and Hydrochlorthiazide in Triamterene-H tablets by multivariate calibration methods.
· Bowers L, Abbott V.10 Evaluation of extraction methods and third generation
HPLC columns for analysis of diuretics.
· Fouracre C, Kazlauskas R.11 Diuretics screening and confirmation using LC MS/MS method.
· Qin Y et al .,12 Application of HPLC-mass spectrometry detection of diuretics
in human urine.
· Stolarczyk M, Apola, Krzek J.13 Analysis of hypotensive compounds occurring in complex agents.
· Mascher H, Wasilewski M.14 Simple and fast HPLC method for the determination of Triamterene and Hydroxytriamterene sulphate in plasma and urine.
· Wageih NE, Abbas SS, Abdelkawy M, Abdelranman MM.15 Specrophotometric and spectrodensitometric determination of Triamterene and Xipamide in pure and in pharmaceutical formulation.
· Jonczyk A, Nowakowska Z.16Determination of Hydochlorthiazide, Triamterene and Propranolol hydrochloride by spectrophotometric method and HPLC.
The above review indicates that there are no simple and economical methods available for the simultaneous estimation of Triamterene and Benzthiazide in bulk and pharmaceutical formulation.
6.4 Objectives of the study :
Literature review showed that there is no analytical work reported for simultaneous estimation of Triamterene and Benzthiazide. In the view of above fact, the following new analytical methods are planned to develop with high sensitivity, accuracy and precision.
In the proposed work attempt shall be made to :
· Develop new analytical methods for simultaneous estimation of Triamterene and Benzthiazide in bulk and combination by UV spectroscopy.
§ Area under curve method.
§ Q – Absorbance ratio.
§ First derivative spectroscopy.
§ Second derivative spectroscopy.
§ Simultaneous equation method (Vierodt’s method)
· Develop new analytical method for simultaneous estimation of Triamterene and Benzthiazide in bulk and combination by HPLC.
· Develop new analytical method for simultaneous estimation of Triamterene and Benzthiazide in bulk and combination by HPTLC.
· Validate the proposed methods in accordance with IP, BP, USP and ICH guidelines for the intended analytical application.
Materials and methods :
7.1 Source of data :
a. Internet – National College of Pharmacy, Shimoga.
b. Kuvempu University Library, Shankaraghatta, Shimoga.
c. IISc library, Bangalore, Karnataka.
d. RGUHS library, Bangalore, Karnataka.
7.2 Method of data collection :
For selection and standardization of mobile phase/s to be used in HPLC, different combination and ratio of solvent will be tried to obtained good optimum resolution. By using retention time and chromatogram of Triamterene and Benzthiazide typical analytical parameters will be determined
For UV spectroscopic estimation we are in need of Shimadzu 1700 double beam spectrophotometer, other Chromatographic instruments and volumetric glass apparatus which are available in the laboratory of Pharmaceutical analysis department, National college of pharmacy, Shimoga.
Journals :
· Acta Poloniae Pharmaceutica – Drug Research
· Chromatographia.
· Postgraduate Medical journal.
· Journal of Pharmaceutical and Biomedical Analysis.
· Journal of Planar Chromatography.
· Indian Journal of Pharmaceutical sciences.
· Indian Journal of Analytical Chemistry and Analyst.
7.3 DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER HUMANS OR ANIMALS?
------NO ------
7.4 HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.3?
------NOT APPLICABLE ------
LIST OF REFERENCES :
1. Foye OW. Principles of medicinal chemistry. 4th ed. BT Waverly Pvt ltd, NewDelhi. 2007:415.
2. Indian Pharmacopoeia. 1996;2:774
3. O’Neil MJ. Merck Index - an encyclopedia of chemicals, drugs and biologicals. 13th ed. New Jersey. 1996:9274 & 1122.
4. Tripati KD. Essentials of Medicinal Pharmacology. Jaypee brother’s medical publications pvt ltd, New Delhi. 2001;4:561-74.
5. Falco CP, Hernandez RH, Cabeza AS. Determination of Triamterene in urine by HPLC using fluorescence detection and column-switching. Chromatographia.
1994;38:29-38.6. Yap B, Kazlauskas R. Rapid HPLC screening of Chlorthiazide, Torasemide, Xipamide and Benzthiazide in Sydney 2000 Olympic Games. Australian Sports Drug Testing Laboratory, Suakin Street, Australia. 2000:209-13.
7. Maslanka A, Krzek J, Stolarczyk. Simultaneous estimation of Hydrochlorthiazide, Triamterene, Furosemide and Spiranolactone by densitometric TLC. J Planar Chromat. 2009;22:405-10.
8. Stolarczyl M, Apola A, Krzek J, Lech K. Simultaneous estimation of Triamterene and Hydrochlorthiazide in tablets using derivative Spectroscopy. Jagiellonian University, Poland. Acta Pol Pharm- DR. 2008;65:283-7.
9. Kargosha K, Sarrafi HM. Spectrophotometric simultaneous estimation of Triamterene and hydrochlorthiazide in Triamterene-H by multivariate calibration methods. J Pharmceut Biomed. 2001;26:273-9.
10. Bowers l, Abbott V. Evaluation of extraction methods and third generation HPLC columns for analysis if Diuretcs. Sports Medicine Drug Identification Laboratory, Indiana, United States. 1991:261-7.
11. Fouracre C, Kazlauskas R. Diuretics screening and confirmation using LC MS/MS method. Australian Sports Drug Testing Laboratory, Australia. 2001:321-6.
12. Qin Y, Wang XB, Wang C, Zhao M, Wu MT, Xu YX, Peng SQ. Application of HPLC-mass spectrometry detection of diuretics in human urine. J Chromatogr B. 2003;794:193-203.
13. Stolarczyk M, Apola, Krzek J. Analysis of hypotensive compounds occurring in complex agents. Acta Pol Pharm- DR. 2010;67:441- 54.
14. Mascher H, Wasilewski M. Simple and fast HPLC method for the determination of Triamterene and Hydroxytriamterene sulphate in plasma and urine. J Liq Chromatogr R T. 1994;17:1577-85.
15. Wageih NE, Abbas SS, Abdelkawy M, Abdelranman MM. Specrophotometric and spectrodensitometric determination of Triamterene and Xipamide in pure and in pharmaceutical formulation. Drug testing and analysis. 2010;2:113-21.
16. Jonczyk A, Nowakowska Z. Determination of Hydochlorthiazide, Triamterene and Propranolol hydrochloride by spectrophotometric method and HPLC. Acta Pol Pharm- DR. 2001;58:339-44.
7