Analytical methods for vancomycin determination in biological fluids and in pharmaceuticals

Vancomycin is a glycopeptide antibiotic employed in the treatment of infections caused by certain methicillin-resistant staphylococci. It is indicated also for patients allergic to penicillin or when there is no response to penicillins or cephalosporins. The adequate vancomycin concentration levels in blood serum lies between 5 and 10 mg/L. Higher values are toxic, causing mainly nephrotoxicity and ototoxicity. Various analytical methods are described in the literature: spectrophotometric, immunologic, biologic and chromatographic methods. This paper reviews the main analytical methods for vancomycin determination in biological fluids and in pharmaceutical preparations.

Recent research data on the removal of pharmaceuticals from sewage treatment plants (STP)

Pharmaceutical compounds have been detected in sewage treatment plant (STP) effluents, surface waters and, less frequently, in groundwater and drinking water, all over the world. Different sources are responsible for their appearance in the aquatic environment, however, it is widely accepted that the main sources of this type of pollutant are STP effluents. The adverse effects of pharmaceuticals in the environment include aquatic toxicity, development of resistance in pathogenic bacteria, genotoxicity and endocrine disruption. Thus, the discharge of these compounds to the environment in STP effluents should be minimized.

A simple square-wave voltammetric method for the determination of scopolamine in pharmaceuticals using a boron-doped diamond electrode

A simple procedure is described for the determination of scopolamine by square-wave voltammetry using a cathodically pretreated boron-doped diamond electrode. Cyclic voltammetry studies indicate that the oxidation of scopolamine is irreversible at a peak potential of 1.59 V (vs. Ag/AgCl (3.0 mol L-1 KCl)) in a 0.50 mol L-1 sulfuric acid solution. Under optimized conditions, the analytical curve obtained was linear (r = 0.9996) for the scopolamine concentration range of 1.0 to 110 µmol L-1, with a detection limit of 0.84 µmol L-1. The method was successfully applied to the determination of scopolamine in pharmaceutical formulations with minimum sample preparation.

Sensitive bromatometric assay methods for finasteride in pharmaceuticals

Three sensitive spectrophotometric methods are presented for the determination of finasteride in bulk and in tablets. The methods rely on the use of bromate-bromide reagent and three dyes namely, methyl orange, indigocarmine and thymol blue as reagents. They involve the addition of a measured excess of bromate-bromide reagent to finasteride in acid medium, and after the bromination reaction is judged to be complete, the unreacted bromine is determined by reacting with a fixed amount of either methylorange and measuring the absorbance at 520 nm (method A) or indigocarmine and measuring the absorbance at 610 nm (method B) or thymol blue and measuring the absorbance at 550 nm (method C). In all the methods, the amount of insitu generated bromine reacted corresponds to the amount of finasteride. The absorbance measured at the respective wavelength is found increase linearly with the concentration of finasteride. Beer's law is obeyed in the ranges 0.25- 2.0, 0.5-6.0 and 1-12 µg mL-1 for method A, method B and method C, respectively. The calculated molar absorptivity values are 5.7x10(4), 3.12x10(4) and 1.77x10(4) L mol-1 cm-1 respectively, for method A, method B and method C, and the corresponding Sandell sensitivity values are 0.0065, 0.012 and 0.021 µg cm-2. The limits of detection (LOD) and quantification (LOQ) are also reported for all the methods. Accuracy and, intra-day and inter-day precisions of the methods were established according to the current ICH guidelines. The methods were successfully applied to the determination of finasteride in commercially available tablets and the results were found to closely agree with the label claim. The results of the methods were statistically compared with those of a reference method by applying Student's t-test and F-test. The accuracy and reliability of the methods were further confirmed by performing recovery tests via standard addition procedure.

Sensitive spectrophotometric determination of lansoprazole in pharmaceuticals using ceric ammonium sulphate based on redox and complex formation reactions

Two simple sensitive and cost-effective spectrophotometric methods are described for the determination of lansoprazole (LPZ) in bulk drug and in capsules using ceric ammonium sulphate (CAS), iron (II), orthophenanthroline and thiocyanate as reagents. In both methods, an acidic solution of lansoprazole is treated with a measured excess of CAS followed by the determination of unreacted oxidant by two procedures involving different reaction schemes. The first method involves the reduction of residual oxidant by a known amount of iron(II), and the unreacted iron(II) is complexed with orthophenanthroline at a raised pH, and the absorbance of the resulting complex measured at 510 nm (method A). In the second method, the unreacted CAS is reduced by excess of iron (II), and the resulting iron (III) is complexed with thiocyanate in the acid medium and the absorbance of the complex measured at 470 nm (method B). In both methods, the amount CAS reacted corresponds to the amount of LPZ. In method A, the absorbance is found to increase linearly with the concentration of LPZ where as in method B a linear decrease in absorbance occurs. The systems obey Beer's law for 2.5-30 and 2.5-25 µg mL-1 for method A and method B, respectively, and the corresponding molar absorptivity values are 8.1×10³ and 1.5×10(4) L mol-1cm-1 . The methods were successfully applied to the determination of LPZ in capsules and the results tallied well with the label claim. No interference was observed from the concomitant substances normally added to capsules.

Spectrophotometric determination of lansoprazole in pharmaceuticals using bromate-bromide mixture based on redox and complexation reactions

Two sensitive spectrophotometric methods are described for the determination of lansoprazole (LPZ) in bulk drug and in capsule formulation. The methods are based on the oxidation of lansoprazole by insitu generated bromine followed by determination of unreacted bromine by two different reaction schemes. In one procedure (method A), the residual bromine is treated with excess of iron (II), and the resulting iron (III) is complexed with thiocyanate and measured at 470 nm. The second approach (method B) involves treating the unreacted bromine with a measured excess of iron (II) and remaining iron (II) is complexed with orthophenanthroline at a raised pH, and measured at 510 nm. In both methods, the amount of bromine reacted corresponds to the amount of LPZ. The experimental conditions were optimized. In method A, the absorbance is found to decrease linearly with the concentration of LPZ (r = -0.9986) where as in the method B a linear increase in absorbance occurs (r = 0.9986) The systems obey Beer's law for 0.5-4.0 and 0.5-6.0 µg mL-1 for method A and method B, respectively. The calculated molar absorptivity values are 3.97µ10(4) and 3.07µ10(4) L mol-1cm-1 for method A and method B, respectively, and the corresponding Sandell sensitivity values are 0.0039 and 0.0013 µg cm-2. The limit of detection (LOD) and quantification (LOQ) are also reported for both methods. Intra-day and inter-day precision, and accuracy of the methods were established as per the current ICH guidelines. The methods were successfully applied to the determination of LPZ in capsules and the results tallied well with the label claim and the results were statistically compared with those of a reference method by applying the Student's t-test and F-test. No interference was observed from the concomitant substances normally added to capsules. The accuracy and validity of the methods were further ascertained by performing recovery experiments via standard-addition method.

Cerimetric determination of simvastatin in pharmaceuticals based on redox and complex formation reactions

Two sensitive spectrophotometric methods are described for the determination of simvastatin (SMT) in bulk drug and in tablets. The methods are based on the oxidation of SMT by a measured excess of cerium (IV) in acid medium followed by determination of unreacted oxidant by two different reaction schemes. In one procedure (method A), the residual cerium (IV) is reacted with a fixed concentration of ferroin and the increase in absorbance is measured at 510 nm. The second approach (method B) involves the reduction of the unreacted cerium (IV) with a fixed quantity of iron (II), and the resulting iron (III) is complexed with thiocyanate and the absorbance measured at 470 nm. In both methods, the amount of cerium (IV) reacted corresponds to SMT concentration. The experimental conditions for both methods were optimized. In method A, the absorbance is found to increase linearly with SMT concentration (r = 0.9995) whereas in method B, the same decreased (r = -0.9943). The systems obey Beer's law for 0.6-7.5 and 0.5-5.0 µg mL-1 for method A and method B, respectively. The calculated molar absorptivity values are 2.7 X 10(4) and 1.06 X 10(5) Lmol-1 cm-1, respectively; and the corresponding sandel sensitivity values are 0.0153 and 0.0039µg cm-2, respectively. The limit of detection (LOD) and quantification (LOQ) are reported for both methods. Intra-day and inter-day precision, and accuracy of the methods were established as per the current ICH guidelines. The methods were successfully applied to the determination of SMT in tablets and the results were statistically compared with those of the reference method by applying the Student's t-test and F-test. No interference was observed from the common excipients added to tablets. The accuracy and validity of the methods were further ascertained by performing recovery experiments via standard addition procedure.

A simple method for the spectrophotometric determination of cephalosporins in pharmaceuticals using variamine blue

A simple spectrophotometric method for the determination of cefotaxime, ceftriaxone, cefadroxil and cephalexin with variamine blue is presented. The determination is based on the hydrolysis of β-lactam ring of cephalosporins with sodium hydroxide which subsequently reacts with iodate to liberate iodine in acidic medium. The liberated iodine oxidizes variamine blue to violet colored species of maximum absorption at 556 nm. The absorbance is measured within the pH range of 4.0-4.2. Beer's law is obeyed in the range of 0.5-5.8 µg mL-1, 0.2-7.0 µg mL-1, 0.2-5.0 µg mL-1 and 0.5-8.5 µg mL-1 for cefotaxime, ceftriaxone, cefadroxil and cephalexin respectively. The analytical parameters were optimized and the method is successfully applied for the determination of cefotaxime, ceftriaxone, cefadroxil and cephalexin in pharmaceuticals.

Spectrophotometric determination of ofloxacin in pharmaceuticals and human urine

Three simple and sensitive spectrophotometric methods are described for the determination of ofloxacin (OFX) in pharmaceuticals and in spiked human urine. First and second methods are based on the measurement of absorbance of OFX in 0.1 M HCl at 293 nm (method A) and 0.1 M NaOH at 287 nm, respectively. The third method is based on the measurement of 2:1 complex formed between OFX and iron(III) in H2SO4 medium, the complex peaking at 420 nm (method C). The optimum conditions for all the three methods are optimized. Beer's law is obeyed over the ranges 0.63-12.5 using method A and method B, and 10-120 µg mL-1 using method C. The apparent molar absorptivity values are calculated to be 3.5 × 10(4), 2.76 × 10(4) and 2.51 × 10³ L mol-1cm-1 for method A, method B and method C, respectively. The Sandell sensitivity, limit of detection (LOD) and limit quantification (LOQ) values are also reported. All the methods were validated in accordance with current ICH guidelines. The developed methods were employed with high degree of precision and accuracy for the estimation of total drug content in commercial tablet formulations of DOX. The results obtained from human spiked urine are satisfactory and recovery values are in the range 95.5-106.6%.

Titrimetric and spectrophotometric assay of bupropion hydrochloride in pharmaceuticals using mercury(II) nitrate

Two simple, rapid and accurate methods for the determination of bupropion hydrochloride (BUP) in pure and in pharmaceutical preparations are described. Both methods are based on the measurement of the chloride of its hydrochloride. In the titrimetric method, the chloride content of bupropion hydrochloride is determined by titrating with mercury(II)nitrate using diphenylcarbazone-bromophenol blue as indicator. Titrimetric method is applicable over a range 2-20 mg of BUP and the reaction stoichiometry is found to be 2:1 (BUP: Hg(NO3)2). The spectrophotometric method involves the addition of a measured excess of mercury(II) nitrate reagent in formate buffer to the drug, and after ensuring the reaction had gone to completion, the unreacted mercury(II) is treated with a fixed amount of diphenylcarbazone, and absorbance measured at 515 nm. The absorbance is found to decrease linearly with increasing concentration of BUP and the calibration curve is linear over 1.0-15.0 µg mL-1 BUP. The proposed methods were successfully applied to the determination of BUP in commercially available dosage forms with good accuracy and precision, and without detectable interference by excipients. The accuracy was further ascertained by placebo blank and synthetic mixture analyses and also by recovery experiments via standard-addition procedure.

Conductometric determination of propranolol hydrochloride in pharmaceuticals

In this paper the conductometric titration of propranolol hydrochloride in pharmaceutical formulations using silver nitrate as titrant is proposed. The method was based on the formation of an insoluble salt (AgCl(s)) between the chloride of propranolol hydrochloride molecule and Ag(I) ions of the titrant AgNO3. The effect of the PROP-AgNO3 concentrations and the interval of time between the successive additions of the titrant on the shape of the titration curve were studied. The obtained recoveries for four samples ranged from 96.8 to 105%. The proposed method was successfully applied in the determination of propranolol hydrochloride in several pharmaceutical formulations, with results in close agreement at a 95 % confidence level with those obtained using official spectrophotometric method.

Avaliação do anticoncepcional Norplant no Município do Rio de Janeiro, RJ (Brasil)

Métodos anticoncepcionais para longo tempo de uso têm sido buscados em vários lugares. O método Norplant é um deles, baseado em cápsulas de levonorgestrel introduzidas no braço das mulheres, através da liberação hormonal diária com efeito de dois a cinco anos. Norplant é produzido sob licença do "Population Council" e industrializado por "Leiras Pharmaceuticals", tendo sido usado na Tailândia, Egito, Indonésia, Suécia, Dinamarca e Brasil. Avaliam-se os resultados deste método, no Município do Rio de Janeiro (Brasil), onde 175 usuárias de Norplant foram entrevistadas em suas casas, e as respostas comparadas com dois grupos-controle (usuárias de pílulas à base de levonorgestrel e usuárias de métodos não-hormonais). Os resultados mostram aumento dos riscos relativos das usuárias de Norplant para desordens menstruais, hipertensão, graves distúrbios de peso e hipertricose, todos estes estatisticamente significantes. Outros achados não significantes foram angina pectoris, encefalopatia hipertensiva, acne e duodenite. Alguns sintomas graves como cefaléia e alterações de comportamento foram mencionados e desapareceram após a retirada das cápsulas. É discutida a relevância de todos os efeitos colaterais em mulheres que decidiram interromper o uso do Norplant. Nestes casos, as medidas de acompanhamento são necessárias, uma vez que hemorragia, ganho de peso acentuado e dificuldades na gravidez podem se desenvolver.

Problems in the regulatory policy of the drug market

OBJECTIVE Analyze the implementation of drug price regulation policy by the Drug Market Regulation Chamber.METHODS This is an interview-based study, which was undertaken in 2012, using semi-structured questionnaires with social actors from the pharmaceutical market, the pharmaceuticals industry, consumers and the regulatory agency. In addition, drug prices were compiled based on surveys conducted in the state of Sao Paulo, at the point of sale, between February 2009 and May 2012.RESULTS The mean drug prices charged at the point of sale (pharmacies) were well below the maximum price to the consumer, compared with many drugs sold in Brazil. Between 2009 and 2012, 44 of the 129 prices, corresponding to 99 drugs listed in the database of compiled prices, showed a variation of more than 20.0% in the mean prices at the point of sale and the maximum price to the consumer. In addition, many laboratories have refused to apply the price adequacy coefficient in their sales to government agencies.CONCLUSIONS The regulation implemented by the pharmaceutical market regulator was unable to significantly control prices of marketed drugs, without succeeding to push them to levels lower than those determined by the pharmaceutical industry and failing, therefore, in its objective to promote pharmaceutical support for the public. It is necessary reconstruct the regulatory law to allow market prices to be reduced by the regulator as well as institutional strengthen this government body.

Spectrophotometric determination of cefaclor in pharmaceutical preparations

A simple spectrophotometric method is proposed for the determination of cefaclor. The method involves alkaline hydrolysis of the drug in ammonia buffer solution at pH 10 to yield diketopiperazine-2,5-dione derivative and subsequent measurement at 340 nm. Beer's law is obeyed in the concentration range 1.8 - 55 mg/mL. The proposed method was successfully applied to the determination of cefaclor in pharmaceutical formulations.

Fármacos no meio ambiente

Pharmaceutical drugs have been detected in sewage treatment plants, surface waters, underground waters and potable waters. Some investigations have been conducted in several countries such as Germany, Brazil, Canada, United States, The Netherlands, England and Italy. Patients and animals excrete part of pharmaceuticals used for human and veterinary medicine after administration in domestic sewage or on the soil. Drugs residues which have not been completely removed during passage through a sewage treatment plant (STP) enter the aquatic environment. The effects of such residual drugs in terrestrial and aquatic organisms are scarcely known.