Medicamentsen-ligne vous propose les traitements dont vous avez besoin afin de prendre soin de votre santé sexuelle. Avec plus de 7 ans d'expérience et plus de 80.000 clients francophones, nous étions la première clinique fournissant du acheter cialis original en France à vente en ligne et le premier vendeur en ligne de Levitra dans le monde. Pourquoi prendre des risques si vous pouvez être sûr avec Medicamentsen-ligne - Le service auquel vous pouvez faire confiance.

Indian J.Pharm. Educ. Res. 41(2), Apr – Jun, 2007
Estimation and pharmacokinetics of metformin in
human volunteers
D. Bhavesh*, G. Chetan, K. M. Bhat1 and Shivprakash
Synchron Research Services Private Limited. Ahmedabad – 380 054 1Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal 576 104 E – mail : ABSTRACT
A simple and rapid HPLC assay method for the estimation of metformin in human plasma was developed and
validated. The method totally eliminates the extraction procedure. The plasma proteins were precipitated using
perchloric acid : acetonitrile (50%v/v) mixture and the supernatant liquid was removed, dried under nitrogen,
reconstituted in mobile phase and injected into the HPLC system. The separation was achieved with a cationic
exchange column (Hihchrom, 250X4.6mm) with mobile phase of methanol: potassium di-hydrogen
orthophosphate buffer (0.1M, pH 3.5) mixture 46 : 54 % v/v and elevated temperature of 40 0 C. Detection was
by UV detector at 236nm. The retention time (RT) observed are at around 13 and 16 minutes for metformin and
phenformin respectively. The response was linear over a range of 30-5000 ng ml-1. The same method was used
for the bioequivalence study of two metformin formulations in healthy, human, Indian, male volunteers

Metformin hydrochloride is an oral biguanidine, which to be more suitable. The same method has also been reduces the elevated blood glucose concentration in utilized for the Bioeequivalence study of metformin patients with diabetes but does not increase insulin secretion. It does not lower the blood glucose in non-diabetic subjects1. Augmentation of muscular glucose uptake and utilization, and reduction of increased hepatic glucose production through an antigluconergic action explain the blood glucose lowering effect2,3. Metformin is safe4 and not teratogenic5 in many of the species studied. Oral bioavailability of metformin is about 50 - 60% and fecal recovery is about 30%6. The rate of absorption was slower than that of elimination, which resulted in a plasma concentration profile of “flip-flop” type for oral MATERIALS AND METHODS
Metformin and phenformin were obtained from Many HPLC methods for the analysis of metformin in Medrich Sterilab, Bangalore, India. Methanol and plasma are reported. But most of the methods use either acetonitrile of HPLC Grade and potassium dihydrogen ion pair reagent8,9,10 or cation exchange column11. Some orthophosphate, glacial acetic acid, ammonium methods reported require elaborate sample hydroxide and perchloric acid of GR Grade were preparation12,13. Though, these methods are sensitive purchased from E. Merck (India) Ltd., Mumbai. and reproducible, RP-HPLC method for the estimation Analysis was performed using Merck Hitachi System containing a pump (L-7100), UV-Visible Detector (L- Indian Journal of Pharmaceutical Education & Research 7400), auto sampler (L-7200) with peltier cooler, Received on 16.09.2005 Modified on 13.06.2006 column oven (L-7350). The data processing was done Accepted on 21.07.2006 APTI All rights reserved
Indian J.Pharm. Educ. Res. 41(2), Apr – Jun, 2007
with the help of MHSM software through D-7000 reconstituted in 100 µl of mobile phase and 80 µl of The analytical column used was cation exchange Method validation
column (NC1005SA, 250X4.6mm Hihchrom). The The linearity of the method was investigated by serially
mobile phase was a mixture of methanol and buffer at
diluting a stock solution of metformin (in methanol; 1.0 the ratio of 46:54% v/v. The buffer was 0.1M mg/ml) with drug free plasma to concentrations in the potassium dihydrogen orthophosphate of pH 3.5 range 30-5000 ng/ml and subjecting 100 µl of each of adjusted with glacial acetic acid or ammonium these solutions to the proposed assay method. hydroxide. The flow rate was maintained at 1.0 ml Calibration curves were constructed by plotting the min-1 and the eluents were monitored at 236nm. The ratio of peak height of metformin to phenformin (Internal Standard) against the concentration of Pharmacokinetic Studies
The test drug metformin hydrochloride (850 mg) of Analyte recovery was determined by comparing the Medrich Sterilab, India and the reference Glycolphage ratio of peak height of metformin to internal standard (850 mg) of Lipha Pharma, UK was procured from for the standard preparations against those of same Medrich Sterilab, India and both test and reference preparations in mobile phase. Interday assay tablet were administered to 12 healthy human male reproducibility was assessed over a period of 4 days at Indian volunteers in a double blind, randomized, cross 100, 3000 and 4750 ng/ml concentration. Intraday over design. The washout period was seven days. The analysis was determined upon replicate analysis of 8 volunteers were selected on pre set inclusion-exclusion criteria. The volunteers were screened for vital signs, blood and urine analysis before enrolment. The tablets The precision of the retention times observed for were administered with 240 ml of potable water at metformin and Internal Standard (n=6), expressed as ambient temperature. 7 ml of blood samples were RSD were less than 0.5%. The representative withdrawn at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 5.0, 6.0, chromatograms of blank human plasma and overlay 8.0, 10.0, 12.0, 18.0, 24.0 hours post dose. The samples chromatograms of three Quality Controls plasma with were stored at –200C for analysis. A concentration time metformin and Internal Standard shown in figure 1 and curve was plotted and Area Under Curve (AUC) was figure 2 respectively indicate that there are no calculated by linear trapezoidal rule (AUC0-ϖ). endogenous interfering components co-eluting with Maximum Plasma Concentration (Cmax) and Time to achieve the maximum concentration (tmax) was obtained Linear regression results for calibration curves directly from the concentration time curve without performed on 4 different days showed mean correlation interpolation. All the pharmacokinetic and statistical coefficients (r2) of more than 0.99 and slope of data were calculated using the software Kinetica. Table1 summarizes the assessment of both interday and Sample Extraction
intraday reproducibility of the method. Data presented 100µl of metformin hydrochloride solution of in table 1 are the coefficients of variability (CV%) for appropriate concentration and 100µl of phenformin each check sample processed. The extraction yield hydrochloride solution (20µg ml-1) were added to 900 (recovery) was calculated by comparing extracted µl of drug free plasma contained in a clean 5 ml Ria samples with unextracted samples at two different Vial and was properly mixed. To this 50 µl of protein concentration levels. The data is given in table 2. precipitating agent (perchloric acid : acetonitrile Absolute recovery of metformin from plasma was 50%v/v each) was added and was vortexed for 30 seconds. After centrifugation at 3000 rpm for 10 Evaluation of the effect of short-term storage of minutes, 700 µl of the supernatant was evaporated to extracted plasma samples on the standard curve dryness at 450C under nitrogen. The residue was characteristics and chromatographic behaviour of Indian J.Pharm. Educ. Res. 41(2), Apr – Jun, 2007
Table 1: Intraday and Interday variability of the assay of quality control samples at three concentration levels.
Table 2: Percent yield in Human Plasma (Metformin)
Table 3: Freeze-Thaw effect on Metformin Recovery
Table 4: Pharmacokinetic Data of Metformin
(ng ml-1) metformin and Internal Standard were also performed. from 0 to 24 h was determined by linear trapezoidal Regression analysis of the standard curve data gave rule. The extrapolation to infinity was calculated using correlation coefficients and values for the slope and Y- a linear regression model from the terminal data points intercept within the same order of magnitude following in the elimination phase that has been log transformed. storage of samples at –200 C from 1 - 4 days. The Maximum concentration achieved (Cmax) was obtained chromatographic behaviour was also unaffected by directly from the measured concentration without storage of extracted plasma samples in auto sampler at interpolation. Assuming the multiplicative models 200C for 12 h. Freeze-thaw analysis of 3 cycles did not expected medians of these parameters of the test and show any major degradation of metformin. The results reference formulations were computed and presented in are shown in table 3. Overlay graph of mean table 4 as their ratios. The confidence intervals suitable concentration v/s time curve of the two formulations for bioequivalence testing were found well within the (Test and Reference) is shown in figure 3. The AUC Indian J.Pharm. Educ. Res. 41(2), Apr – Jun, 2007
Retention Time (min)
Figure 1: Representative chromatogram of blank
Figure 2: Overlain chromatogram of three Quality
human plasma
a ________Chromatogram of LQC
b ____ _ _ Chromatogram of MQC
c ------------Chromatogram of HQC

Figure 3: Mean concentration v/s time curve of the two formulations
2. Bailey C. J. Biguanides and NIDDM. Diabetes The HPLC assay method described here is simple, precise and accurate for quantitation of metformin in 3. Hermann L. S. Metformin: a review of its human plasma. The sensitivity, simplicity and rapidity pharmacological properties and therapeutic of the method were the main advantages of the method. use. Diabete metab. 1979 Sep; 5(3): 233-45. The method was cross checked by different analyst and 4. Duval D. 1959 Pharmacological study of equipment and was found to be rugged and robust. The N,N,Dimethyl guanyl guanidine (LA 6023), method can be conveniently used for the therapeutic monitoring and pharmacokinetic studies of metformin. REFERENCES
biguanidine class of oral hypoglycemic agents 1. Hermann L. S. Clinical Pharmacology of on mouse embryogenesis. Teratology. 1994 biguanides, In: Kulhmann I, Plus W editor. 6. Tucker G. T., Casey C, Philips P. J, Connor H, Hiedelberg: Springer Veelog; 1995. p. 374 - kinetics in healthy subjects and in patients with diabetes mellitus. British J. of clinical Indian J.Pharm. Educ. Res. 41(2), Apr – Jun, 2007
7. Pentikainen P. J., Neuvonen P. J., Pentilla A. 11. Bonfigli A. R, Manfrini S, Gregorio F, Testa R, Testa I, De Sio G, Coppa G. Determination intravenous and oral administration to man. of plasma Metformin by new cation exchange Eur. J. Clin. Pharmacol. 1979 Sep; 16(3): 683- 8. Zarghi A., Foroustan S. M, Shafaati A, Metformin in human plasma using ion-pair high-performance liquid chromatography after HPLC. J. Pharm Biomed Anal. 2003 Feb. 5; ultrafiltration. J. Chromatogr B Biomed Sci 9. Zhang M, Moore G. A, Lever M, Gardiner S. 13. Zhouping Wang, Zhujan Zhang, Zhifeng Fu, J, Kirkpatric C. M, Begg E. J. Rapid and injection Chemiluminescence Determination chromatography assay for the determination of of Metformin based on N-Bromosuccinimide- Metformin in human plasma and breast milk. flourescein System. Analytical Letters. 2001 J. Chromatogr B Analyt Technol Biomed Life 10. Cheng C. L, Chou C. H. Determination of spectrophotometric determination. J. Chromatogr B Biomed Sci Appl. 2001 Oct. 5; 762(1) 51-58. ********


Microsoft word - stoccaggio farmaci errori bis lavoro definitivo.doc

IL FARMACO IN REPARTO: DICEMBRE/’07 RACCOMANDAZIONI Gestione del rischio clinico legato alle terapie Il percorso sicuro del farmaco dall’approvvigionamento allo stoccaggio Aquilanti Luigi Canonici Martina Farmacista Specializzanda Ospedale Belcol e Viterbo Dell’Orso Bruna Modesti Luciano Coordinatore assistenziale Ortopedia Ospedale Tarquinia To

Diet and nutritional status of children with food allergies

F O O D A L L E R G Y A N D A N A P H Y L A X I SDiet and nutritional status of children with food allergiesSophie Flammarion1, Clarisse Santos1, Dominique Guimber2, Lyne Jouannic3,Caroline Thumerelle1, Fre´de´ric Gottrand2 & Antoine Deschildre11Unite´ de pneumologie et allergologie pe´diatriques, de´partement de pe´diatrie, ho´pital Jeanne de Flandre, CHRU de Lille, France, 2Unite

Copyright © 2010-2014 Pharmacy Pills Pdf