Focus on centrin in normal and altered human spermatozoa.

This review provides details on the role of centrin in human spermatozoa and in various forms of male infertility. Centrin is a calcium (Ca2+)-binding phosphoprotein that is located in the centrioles - which are typical structures of the sperm connecting piece and play a key role in centrosome dynamics during sperm morphogenesis - as well as in zygotes and early embryos during spindle assembly. In humans, three different centrin genes encoding three isoforms have been discovered. Centrin 1, the only one expressed in spermatozoa, seems to be lost inside the oocyte after fertilization. The sperm connecting piece is characterized by the presence of numerous proteins including centrin, that deserves particular attention because, in humans, it is enriched during maturation of the centrioles. In normal sperm, centrin 1 is visible as two distinct spots in the head-tail junction; however, in some defective spermatozoa, centrin 1 distribution is altered. Centrin has been studied in humans and animal models. Its mutations may lead to several structural alterations, such as serious defects in the connective piece and, subsequently, fertilization failure or incomplete embryonic development. However, the effects of these abnormalities on male fertility have not been fully studied. Because the presence and the function of centrin in the sperm connecting piece appears important for reproductive success, additional studies are needed to bring medical benefits in resolving some cases of idiopathic infertility.

Validity of caregivers' reports on prior use of antibacterials in children under five years presenting to health facilities in Gulu, northern Uganda.

INTRODUCTION: Given the frequent initiation of antibacterial treatment at home by caregivers of children under five years in low-income countries, there is a need to find out whether caregivers' reports of prior antibacterial intake by their children before being brought to the healthcare facility are accurate. The aim of this study was to describe and validate caregivers' reported use of antibacterials by their children prior to seeking care at the healthcare facility. METHODS: A cross sectional study was conducted among children under five years seeking care at healthcare facilities in Gulu district, northern Uganda. Using a researcher administered questionnaire, data were obtained from caregivers regarding reported prior antibacterial intake in their children. These reports were validated by comparing them to common antibacterial agents detected in blood and urine samples from the children using liquid chromatography with tandem mass spectrometry (LC-MS/MS) methods. RESULTS: A total of 355 study participants had a complete set of data on prior antibacterial use collected using both self-report and LC-MS/MS. Of the caregivers, 14.4% (51/355, CI: 10.9-18.5%) reported giving children antibacterials prior to visiting the healthcare facility. However, LC-MS/MS detected antibacterials in blood and urine samples in 63.7% (226/355, CI: 58.4-68.7%) of the children. The most common antibacterials detected from the laboratory analysis were cotrimoxazole (29%, 103/355), ciprofloxacin (13%, 46/355), and metronidazole (9.9%, 35/355). The sensitivity, specificity, positive predictive value (PPV), negative predictive value and agreement of self-reported antibacterial intake prior to healthcare facility visit were 17.3% (12.6-22.8), 90.7% (84.3-95.1), 76.5% (62.5-87.2), 38.5% (33.0-44.2) and 43.9% (k 0.06) respectively. CONCLUSION: There is low validity of caregivers' reports on prior intake of antibacterials by these children. There is need for further research to understand the factors associated with under reporting of prior antibacterial use.

Quality assessment of selected co-trimoxazole suspension brands marketed in Nairobi County, Kenya.

INTRODUCTION: Quality of medicines in both developed and developing countries is sometimes compromised due to infiltration of counterfeit, substandard or degraded medicines into the markets. It is a public health concern as poor quality medicines endanger public health where patients are exposed to chemical toxins and/or sub-therapeutic doses. This could lead to reduced treatment efficacy and promote development of drug resistance. Co-trimoxazole, a fixed dose combination of sulfamethoxazole and trimethoprim, is a broad spectrum for bacterial diseases and is also used as a prophylaxis for opportunistic infections in HIV infected individuals. This study evaluated quality of selected co-trimoxazole suspension brands marketed in Nairobi County, Kenya. METHODS: A total of 106 samples were collected, categorized into 15 brands and evaluated for active pharmaceutical ingredient content (API) and pH following United States Pharmacopeia. Assay for API was conducted using High Performance Liquid Chromatography. Results were compared with pharmacopeia references. Visual examination of labels and confirmation of retention status of the brands with Pharmacy and Poisons Board retention register was carried out. RESULTS: The samples were primarily of local origin (86.7%). On October 23, 2019, retention status of six of the fifteen brands documented were no longer listed in the Pharmacy and Poisons Board retention register. Of the 106 samples tested 70.6% and 86.8% were compliant with United States Pharmacopeia (USP) specifications for pH and API respectively while 84.0% adhered to packaging and labelling requirements. CONCLUSION: This study has demonstrated that majority of co-trimoxazole suspensions tested were compliant with USP requirements. Additionally, it has provided evidence of poor quality co-trimoxazole medicines that could compromise treatment of infectious diseases in children. This emphasizes the need for regular quality assurance tests to ensure only quality medicines are in the market.

Determination of amoxicillin and cotrimoxazole concentrations in sputum of patients with cystic fibrosis.

In the management of cystic fibrosis, treatments against Staphylococcus aureus and Haemophilus influenzae such as amoxicillin or cotrimoxazole have to be prescribed and the antibiotherapy's efficacy may be linked to the concentration that reaches the infected site. As cystic fibrosis patients present disturbed pharmacokinetics parameters, drug monitoring would be relevant to assess the lung distribution of antibiotics and to optimize dosing regimens. In this context, the aim of the study was to develop and validate HPLC-based methods for the determination of both antibiotics in bronchial sputum from cystic fibrosis patients, in order to assess the distribution of the drugs into the lungs. Plasma proteins were precipitated by acetonitrile and amoxicillin concentrations in sputum were determined by HPLC coupled with tandem-mass spectrometry. Following liquid extraction with ethyl acetate, cotrimoxazole was quantified by HPLC using ultraviolet detection. Both methods were rapid, specific, accurate and reproducible. The method was applied to patient samples. In three treated patients, concentrations of amoxicillin in sputum were similar and below the lower limit of quantification (0.1 µg/g) and in six patients, sputum concentrations up to 11.1 and 6.4 µg/g were measured for sulfamethoxazole and trimethoprim, respectively.

Egg residue and depletion in Rhode Island Red hens (Gallus gallus domesticus) following multiple oral doses of trimethoprim-sulfamethoxazole.

Sulfamethoxazole-Trimethoprim residues in eggs can cause risks to human health. The most common cause of residues in eggs results from failure to meet an appropriate withdrawal interval. The aim of this study was to determine the quantity and duration of sulfamethoxazole-trimethoprim residues in eggs and evaluate the drug elimination parameters in egg components and whole egg to better estimate the withdrawal interval of sulfamethoxazole and trimethoprim following oral administration for 7 days at a purposed dosage regimen (time average 46 mg kg-1 day-1 for sulfamethoxazole, time average 25 mg kg-1 day-1 for trimethoprim). Residues of sulfamethoxazole and trimethoprim in albumen and yolk were analyzed by ultra-performance liquid chromatography mass spectrometry. A greater percentage of sulfamethoxazole was distributed into the albumen (91.53-96.74%) and a greater percentage of trimethoprim was distributed into yolk (63.92-77.36%) during treatment. The residues levels in whole egg declined below or reached the limit of quantification until 13 days for SMZ and TMP respectively. The withdrawal interval for SMZ and TMP were 43 days and 17 days respectively using the FDA tolerance method.

Use of thin-layer chromatography to detect counterfeit sulfadoxine/pyrimethamine tablets with the wrong active ingredient in Malawi.

BACKGROUND: Substandard and falsified anti-malarial medicines pose a serious threat to public health, especially in low-income countries. Appropriate technologies for drug quality analysis in resource-limited settings are important for the surveillance of the formal and informal drug market. The feasibility of thin-layer chromatography (TLC) with different solvent systems was tested using the GPHF Minilab in a study of the quality of sulfadoxine/pyrimethamine tablets in Malawi. METHODS: Twenty eight samples of sulfadoxine/pyrimethamine tablets were collected from randomly selected health facilities of four districts of southern Malawi. A mystery shopper approach was used when collecting samples from illegal street vendors, and an overt approach for the other facilities. Samples were subjected to visual inspection, disintegration testing and TLC analysis. 10 samples were further investigated according to the methods of the US Pharmacopeia using high performance liquid chromatography (HPLC). RESULTS: One sample was found to be falsified, containing a mixture of paracetamol tablets and co-trimoxazole tablets. These had been repackaged into paper strip packs labelled as a brand of sulfadoxine/pyrimethamine. TLC with different solvent systems readily proved that these tablets did not comply with their declaration, and provided strong evidence for the active pharmaceutical ingredients which were actually contained. Full pharmacopeial analysis by HPLC confirmed the results suggested by TLC for this sample, and showed two further samples to be of substandard quality. CONCLUSIONS: Due to the absence of the declared anti-malarial ingredients and due to the presence of other pharmaceutical ingredients, the identified falsified medicine represents a serious health risk for the population. Thin-layer chromatography (TLC) using different solvent systems proved to be a powerful method for the identification of this type of counterfeiting, presenting a simple and affordable technology for use in resource-limited settings.

In-vitro evaluation of the quality of paracetamol and co-trimoxazole tablets used in Malawi based on pharmacopoeial standards.

OBJECTIVES: This study was an in-vitro evaluation of different brands of paracetamol and cotrimoxazole tablets, used or found in Malawi, based on Pharmacopoeia standards, in order to ascertain the existence and extent of substandard medicines in Malawi and to give an overview of their distribution in the public and private sectors. METHODOLOGY: A cross-sectional analytical study was conducted using 11 samples each of paracetamol and cotrimoxazole tablets. Stratified random sampling was used to collect samples. Samples were analyzed using HPLC and Spectrophometric methods as outlined in the BP-2007 and USP-32 at the National Drug Quality Control Laboratory (NDQCL)-Lilongwe (under Pharmacy Medicines and Poisons Board-PMPB) and Orient Pharma Co. Ltd of Taiwan. The results were analyzed using Epi Info. RESULTS AND DISCUSSION: Fifty percent of samples (n=22) were not registered in the country by the PMPB as required by the PMP Act with the majority of those coming from public health facilities. All paracetamol and cotrimoxazole samples complied with identification tests using spectrophotometric and HPLC method. Overall, 27.3% of samples failed to meet the BP-2007 standards for Active Ingredient content, while 22.7% of the samples failed the Friability test. The results from Malawi are similar in magnitude to those within surrounding countries in Africa. CONCLUSION: This pilot study provides objective evidence to show that substandard and unregistered paracetamol and cotrimoxazole are present and being used in Malawi, and thus posing a considerable hazard to public health in Malawi. PMPB, together with the Ministry of Health, must continue to develop a quality assurance system to ensure that medicines are randomly and routinely checked.

A cross-sectional investigation of the quality of selected medicines in Cambodia in 2010.

BACKGROUND: Access to good-quality medicines in many countries is largely hindered by the rampant circulation of spurious/falsely labeled/falsified/counterfeit (SFFC) and substandard medicines. In 2006, the Ministry of Health of Cambodia, in collaboration with Kanazawa University, Japan, initiated a project to combat SFFC medicines. METHODS: To assess the quality of medicines and prevalence of SFFC medicines among selected products, a cross-sectional survey was carried out in Cambodia. Cefixime, omeprazole, co-trimoxazole, clarithromycin, and sildenafil were selected as candidate medicines. These medicines were purchased from private community drug outlets in the capital, Phnom Penh, and Svay Rieng and Kandal provinces through a stratified random sampling scheme in July 2010. RESULTS: In total, 325 medicine samples were collected from 111 drug outlets. Non-licensed outlets were more commonly encountered in rural than in urban areas (p < 0.01). Of all the samples, 93.5% were registered and 80% were foreign products. Samples without registration numbers were found more frequently among foreign-manufactured products than in domestic ones (p < 0.01). According to pharmacopeial analytical results, 14.5%, 4.6%, and 24.6% of the samples were unacceptable in quantity, content uniformity, and dissolution test, respectively. All the ultimately unacceptable samples in the content uniformity tests were of foreign origin. Following authenticity investigations conducted with the respective manufacturers and medicine regulatory authorities, an unregistered product of cefixime collected from a pharmacy was confirmed as an SFFC medicine. However, the sample was acceptable in quantity, content uniformity, and dissolution test. CONCLUSIONS: The results of this survey indicate that medicine counterfeiting is not limited to essential medicines in Cambodia: newer-generation medicines are also targeted. Concerted efforts by both domestic and foreign manufacturers, wholesalers, retailers, and regulatory authorities should help improve the quality of medicines.

Influence of NAT2 polymorphisms on sulfamethoxazole pharmacokinetics in renal transplant recipients.

The sulfamethoxazole (SMX)-trimethoprim drug combination is routinely used as prophylaxis against Pneumocystis pneumonia during the first 3 to 6 months after renal transplantation. The objective of this study was to examine the impact of N-acetyltransferase 2 (NAT2) and CYP2C9 polymorphisms on the pharmacokinetics of SMX in 118 renal transplant recipients. Starting on day 14 after renal transplantation, patients were administered 400 mg/day-80 mg/day of SMX-trimethoprim orally once daily. On day 14 after the beginning of SMX therapy, plasma SMX concentrations were determined by a high-performance liquid chromatography method. The SMX area under the concentration-time curve from 0 to 24 h (AUC(0-24)) for 15 recipients with the NAT2 slow acetylator genotype (NAT2 5/ 6, - 6/ 6, - 6/ 7, and - 7/ 7) was significantly greater than that for 56 recipients with the NAT2 rapid acetylator genotype (homozygous for NAT2 4) (766.4 ± 432.3 versus 537.2 ± 257.5 µg-h/ml, respectively; P = 0.0430), whereas there were no significant differences in the SMX AUC(0-24) between the CYP2C9 1/ 1 and - 1/ 3 groups. In a multiple regression analysis, the SMX AUC(0-24) was associated with NAT2 slow acetylator polymorphisms (P = 0.0095) and with creatinine clearance (P = 0.0499). Hepatic dysfunction in NAT2 slow acetylator recipient patients during the 6-month period after SMX administration was not observed. SMX plasma concentrations were affected by NAT2 polymorphisms and renal dysfunction. Although standard SMX administration to patients with NAT2 slow acetylator polymorphisms should be accompanied by monitoring for side effects and drug interaction effects from the inhibition of CYP2C9, SMX administration at a low dose (400 mg) as prophylaxis may not provide drug concentrations that reach the level necessary for the expression of side effects. Further studies with a larger sample size should be able to clarify the relationship between SMX plasma concentration and side effects.

Development and validation of an HPLC method for simultaneous determination of trimethoprim and sulfamethoxazole in human plasma.

The combination of trimethoprim (TMP) and sulfamethoxazole (SMX) is used in the treatment of many common infections such as urinary, respiratory and gastrointestinal tract infections. The aim of this study was to determine TMP and SMX simultaneously in human plasma samples by high performance liquid chromatography (HPLC) using antipyrine as the internal standard. Separation of the compounds was achieved on a reverse-phase C8 column packed with 5 microm dimethyl octadecylsilyl bonded amorphous silica (4.6 mm x 250 mm) column using a mobile phase consisted of potassium hydrogen phosphate, acetonitrile, methanol and water adjusted to pH 6.2. The mobile phase was delivered at a flow rate of 1 mL min- and the effluent was monitored using Max plot technique at 25 derees C. Retention times were 5 min for TMP, 7 min for antipyrine and 9 min for SMX. Quantitation limits were 10 ng mL(-1) for TMP and 50 ng mL(-1) for SMX. Our findings indicated that the developed HPLC method was precise, accurate, specific and sensitive for simultaneous determination of TMP and SMX. Proposed HPLC method was successfully applied for the analysis of TMP and SMX in human plasma after oral administration of a co-trimoxazole tablet to human volunteers.

Simultaneous determination of sulphamethoxazole and trimethoprim in powder mixtures by attenuated total reflection-Fourier transform infrared and multivariate calibration.

A partial least-squares calibration (PLS) procedure in combination with infrared spectroscopy has been developed for simultaneous determination of sulphamethoxazole (SMZ) and trimethoprim (TMP) in raw material powder mixtures used for manufacturing commercial pharmaceutical products. Multivariate calibration modeling procedures, interval partial least squares (iPLS) and synergy partial least squares (siPLS), were applied to select a spectral range that provided the lowest prediction error in comparison to the full-spectrum model. The experimental matrix was constructed using 49 synthetic samples and 15 commercial samples. The considered concentration ranges were 400-900 mg g(-1) SMZ and 80-240 mg g(-1) TMP. Spectral data were recorded between 650 and 4000 cm(-1) with a 4 cm(-1) resolution by Fourier transform infrared spectroscopy coupled with attenuated total reflectance (ATR-FTIR) accessory. The proposed procedure was compared with conventional procedure by high performance liquid chromatography (HPLC) using 15 commercial samples containing SMZ and TMP. The results showed that PLS regression model combined to ATR-FTIR is a relatively simple, rapid and accurate procedure that could be applied to the simultaneous determination of SMZ and TMP in routine quality control of powder mixtures. A root mean square error of prediction (RMSEP) of 13.18 mg g(-1) for SMZ and 6.03 mg g(-1) for TMP was obtained after selection of better intervals by siPLS. Using the proposed procedure it is possible to analyze each sample in less than 3 min considering two replicates (excluding the grinding step). Accuracy was checked by comparison to HPLC method and agreement better than 98.8% was achieved.

Simultaneous determination of sulfamethoxazole and trimethoprim in biological fluids for high-throughput analysis: comparison of HPLC with ultraviolet and tandem mass spectrometric detection.

The comparison of two methods based on online solid phase extraction-liquid chromatography with UV (SPE-LC-UV) or mass spectrometry detection (SPE-LC-MS/MS) for the simultaneous quantification of sulfamethoxazole (SMZ) and trimethoprim (TMP) is presented. The methods were validated and proved to be accurate. The analysis of standard samples for SMZ at concentrations of 0.5, 1.5, 25 and 50microg/mL demonstrated a relative standard deviation of less than 6% for both methods (n=18), while TMP samples at concentrations of 0.05, 0.15, 1.5 and 5.0microg/mL were analyzed with R.S.D. of less than 4% (n=18). The method with mass spectrometric detection was approximately six times more sensitive than the method with ultraviolet detection. The total run time for the SPE-LC-MS/MS was 2.5min per sample as opposed to 18.0min for the SPE-LC-UV method. The method with MS detection in comparison with UV detection proved to be more rugged and was successfully applied to pharmacokinetics studies.

Determination of antibiotics in aquatic environment by solid-phase extraction followed by liquid chromatography-electrospray ionization mass spectrometry.

A robust and sensitive solid-phase extraction followed by liquid chromatography-electrospray ionization mass spectrometric (LC-ESI-MS) method for determination of antibiotics viz., fluoroquinolones, sulfamethoxazole, trimethoprim and cephalosporines in surface waters was developed. The sample recoveries on Oasis HLB cartridges were found to be >80%. Identification was carried out by LC-ESI-MS/MS. The positive ion ESI mass spectra containing the peaks of quasimolecular ions [M+H](+) allowed the determination of molecular masses whereas the fragment ions obtained by MS/MS of [M+H](+) ions permitted the structural assignment. Quantification was carried out by selective ion monitoring (SIM) using the quasimolecular ions [M+H](+) of the parent compounds. The detection and quantification limits were found to be in the range of 0.6-8.1 and 2.0-24.0 microg/L. The surface waters of different lakes and tanks of Hyderabad, India were found to contain a few antibiotics.

Assessment of MEKC suitability for residue drug monitoring on pharmaceutical manufacturing equipment.

The suitability of micellar electrokinetic chromatography for the simultaneous trace determination of several compounds (sulfamethoxazole, trimethoprim, sulfanilic acid, sulfanilamide, 3,4,5-trimethoxybenzoic acid and nonoxynol-9) was assessed. The mixture was separated within 14min at an applied voltage of 22kV by using 30mM phosphate electrolyte, containing 10mM SDS, adjusted to pH 7.8. Under optimized separation conditions acceptable levels of linearity, precision and accuracy were obtained for all compounds. The method could be used as part of a cleaning validation study when assaying trace levels of co-trimoxazole drug, some of its decomposition products and detergent in the swab samples collected from pharmaceutical manufacturing equipment, after cleaning.

Amoxicillin-clavulanic acid and trimethoprim- sulfamethoxazole in rodent feed and water: effects of compounding on antibiotic stability.

We assessed the concentrations of 2 antibiotic combinations, amoxicillin-clavulanic acid and trimethoprim-sulfamethoxazole when compounded in reverse osmosis [RO] (pH 6.0), tap (pH 6.7), and acidified water (pH 2.6) over 7 d, and pre- and post-pelleting, post-gamma irradiation and shipping, and monthly until 180 d post-milling in feed. Amoxicillin concentrations in RO and tap water varied between 1.18 and 1.29 mg/ml, and 1.09 and 1.22 mg/ml, respectively. The concentration of amoxicillin declined immediately and remained between 0.43 and 0.50 mg/ml in acidified water. Clavulanic acid exhibited a slow time-dependent decrease in concentration to 0.05 mg/ml at day 7 in RO water, immediately declined and varied from 0.02 to 0.05 mg/ml in tap water, and was undetectable in acidified water. Trimethoprim and sulfamethoxazole concentrations were near expected in RO, tap, and acidified water. In food, amoxicillin, trimethoprim, and sulfamethoxazole concentrations were each reduced to approximately 60% of expected after pelleting, but remained stable thereafter for 180 d. The initial clavulanic acid concentration in feed was less than 10% of expected and was undetectable after 1 mo. Plasma drug concentrations were determined in C57BL/6NCrl mice at 4 h after commencement of the dark and light cycles following administration of antibiotic food for at least 72 h. Plasma amoxicillin and sulfamethoxazole concentrations were 3- and 10-fold greater, respectively, during the dark period. Plasma levels of clavulanic acid and trimethoprim were consistent at both time points. These results indicate that the antibiotic concentration can be influenced by compounding in feed and water, and differs in plasma during the light and dark phases of the photoperiod.

Simultaneous determination of trimethoprim and sulphamethoxazole in veterinary formulations by chromatographic multivariate methods.

A comparative chromatographic study was developed for the simultaneous quantitative resolution of trimethoprim (TMP) and sulphamethoxazole (SMX) in veterinary formulations. Multi-wavelength chromatograms were recorded by using diode array detector (DAD) system at the five-wavelength set consisting of 220, 230, 240, 250 and 260 nm. In the first step, five different calibration equations at the above wavelengths for each drug were obtained by using the relationship between concentration and peak area. These calibration graphs were used for the quantitative evaluation of TMP and SMX in samples. These single-wavelength applications were called traditional LC method. In the second step, principal component regression (PCR) and partial least-squares (PLS) calibrations were applied to the above mentioned multi-wavelength chromatograms. The amount of two investigated drugs in samples was determined by the constructed PCR and PLS calibrations. The experimental results obtained from each single-wavelength calibration graph were compared with those obtained by the chemometric approaches and chromatographic multivariate approaches give successful results more than traditional LC method.

Enhanced stability of sulfamethoxazole and trimethoprim against oxidation using hydroxypropyl-beta-cyclodextrin.

The effect of hydroxypropyl-beta-cyclodextrin (HPbetaCD) on the chemical stability of sulfamethoxazole and trimethoprim (co-trimoxazole) under oxidation stress at 50 +/- 2 degrees C was investigated. The concentrations of sulfamethoxazole and trimethoprim in aqueous solutions (pH 5.4) containing 0, 1%, 2%, 5%, 10% and 15% w/v hydroxypropyl-beta-cyclodextrin were measured by HPLC. Both sulfamethoxazole and trimethoprim degradation appeared to follow pseudo-first order kinetics in the presence and in the absence of hydroxypropyl-beta-cyclodextrin. The observed half-lives for sulfamethoxazole and trimethoprim in 15% w/v hydroxypropyl-beta-cyclodextrin were 910 h and 609 h respectively, 11.8 and 3.4 times greater than in solutions without hydroxypropyl-beta-cyclodextrin. Using a Lineweaver-Burk equation, the half-lives for sulfamethoxazole and trimethoprim outside the complex in a solution containing 15% w/v hydroxypropyl-beta-cyclodextrin were estimated at 77 h and 193 h respectively, whereas inside the complex the half-lives were estimated at 850 h and 821 h. In terms of relative increases in stability under oxidation stress the half-lives for sulfamethoxazole and trimethoprim inside the complex were 11.0 times and 4.2 times greater than their half-lives outside the complex. In conclusion, chemical stability of sulfamethoxazole and trimethoprim in co-trimoxazole aqueous solutions under oxidation stress at 50 +/- 2 degrees C can be increased using hydroxypropyl-beta-cyclodextrin as a molecular inclusion excipient.

Automated simultaneous triple dissolution profiles of two drugs, sulphamethoxazole-trimethoprim and hydrochlorothiazide-captopril in solid oral dosage forms by a multicommutation flow-assembly and derivative spectrophotometry.

This article deals with the simultaneous determination of three dissolution profiles with the aid of the new and emerging continuous-flow methodology known as multicommutation. This methodology is based on a flow network of a set of solenoid valves controlled by the computer and acting as independent multicommutators to allow the easy and automated control of flowing solutions. The obtained three dissolution profiles from one dosage form are the whole formulation profile or "global profile" recommended by pharmacopoeias, and, at same time, are recorded two "individual" profiles from two drugs present in the formulation. This is the second attempt to obtain simultaneously three dissolution profiles with a single spectrophotometric detector and the first with the multicommutation methodology. The selected pharmaceutical formulations contained a couple of active principles with overlapped spectra, namely sulphamethoxazole and trimethoprim or hydrochlorothiazide and captopril. The obtained empirical plots profiles fitted with the Higuchi equation also known as the three-parameter equation.

Simultaneous determination of binary mixtures of trimethoprim and sulfamethoxazole or sulphamethoxypyridazine by the bivariate calibration spectrophotometric method.

The bivariate calibration algorithm was applied to the spectrophotometric simultaneous determination of trimethoprim (TMP), sulfamethoxazole (SMX) or sulphamethoxypyridazine (SMP) binary mixtures in pharmaceutical and veterinary products. The results obtained were compared with those from derivative spectrophotometry. The statistical evaluation of the method bias showed that the proposed procedure is comparable with commonly used first-derivative spectrophotometry. However, the advantage of bivariate calibration is its simplicity, due to the minimal spectra manipulation when compared with derivative techniques.

The optimum pH for the derivative spectrophotometric determination of co-trimoxazole in binary mixtures.

BACKGROUND: Although the experimental assessment of co-trimoxazole by use of derivative spectrophotmetry underscores the usefulness of this method due to its relative simplicity with which it can be carried out over the official United States Pharmacopoeia (USP) high pressure liquid chromatography (hplc) methods for this drug, suitable optimum conditions ought to be refined for its universal acceptability. OBJECTIVE: The objective of the present work was to obtain the optimum pH level for the UV assessment of co-trimoxazole. METHODS: The aqueous solutions of the individual drugs and their binary mixtures were buffered with Sodium Acetate-Acetic Acid buffer in the pH ranges 2-7 and scanned on zero order and on first-order derivative at the wave length between 200- 300 nm. RESULTS: At the same drug solution concentrations, spectral shifts occurred with change in pH, especially between the wavelengths 200 and 240 nm, only seeming to converge from approximate wavelength 260 nm onwards. Absorbance fluctuations were also observed at the same drug concentrations in the pH range 2 to 3.5 and 5 to 7 when the solutions were scanned, even at the wavelength where the spectra seem to converge. However there were no absorbance differences between pH 4 and 5. CONCLUSION: The UV spectrophotometric method is dependent on the optimum pH and this has been found to range from 4 to 5.