Simultaneous Quantification of Lamivudine, Zidovudine and Related Impurities in Fixed Oral Dosage Combination Using RP-HPLC with DAD detection

A simple and fast isocratic Reverse Phase High Performance Liquid Chromatography (RP-HPLC) method has been developed and validated for the simultaneous determination of Lamivudine, zidovudine and their related impurities in tablets. The method consists of a mobile phase combination of Acetonitrile (HPLC grade) and Buffer (0.0680 g of Potassium Dihydrogen Orthophosphate, 0.3 ml of Triethylamine, pH adjusted to 8.0 with Orthophosphoric acid to a final volume preparation of 100 ml) in the ratio 10:90. Phenomenex Luna 5-µm C18 (2)-250 x 4.6-mm, 5-µm) was used as the stationary phase. The column oven was set to a temperature of 30±1oC. Quantification was achieved with a DAD detector set at 270 nm. Resolution was achieved at a short run time of 25 minutes. Zidovudine related impurity C, Lamivudine, salicylic acid, Zidovudine and Zidovudine related impurity B eluted at 3.749±0.004, 4.862±0.013, 15.332±0.064, 21.201±0.076 and 23.682±0.117 respectively. Relative retention times (RRT) for lamivudine unknown related impurities with respect to Zidovudine were 0.15, 0.17, 0.30 and 0.59. RRT for Zidovudine unknown related impurities with respect to Zidovudine were 0.39 and 0.63.  The method was found to be specific, robust, accurate and precise for the estimation of Zidovudine related impurity C, Lamivudine, salicylic acid, Zidovudine and Zidovudine related impurity B in fixed oral dosage tablets over the concentration ranges of 0.0204 mg/mL-0.0088 mg/mL, 0.0962 mg/mL-0.7699 mg/mL, 0.1929 mg/mL-1.5410 mg/mL and 0.0088 mg/mL-0.024 mg/mL respectively. The Correlation Coefficient (r2) for Zidovudine related impurity C, Lamivudine, salicylic acid, Zidovudine and Zidovudine related impurity B were greater than 0.998. The LOD were found to be between 1.9x10-4 mg/mL to 2.69 x10-4 mg/mL.  The proposed method is precise, specific, accurate and robust for the simultaneous estimation of Zidovudine related impurity C, Lamivudine, salicylic acid, Zidovudine, Zidovudine related impurity B and other related impurities in dosage forms. Keywords: Zidovudine related impurity C, Lamivudine, salicylic acid, Zidovudine, Zidovudine related impurity B, Lamivudine related impurities, Zidovudine related impurities RP-HPLC, Validation.

Relative Response Factor for Lamivudine and Zidovudine Related substances by RP-HPLC with DAD detection

A study was conducted to establish the Relative Response Factors for Zidovudine related impurity C, Lamivudine salicylic acid and Zidovudine related impurity B.  A simple and fast isocratic Reverse Phase High Performance Liquid Chromatography (RP-HPLC) method was used for the simultaneous determination of the related impurities. The method consists of a mobile phase combination of Acetonitrile (HPLC grade) and Buffer (0.0680 g of Potassium Dihydrogen Orthophosphate, 0.3 ml of Triethylamine, pH adjusted to 8.0 with Orthophosphoric acid to a final volume preparation of 100 ml) in the ratio 10:90 using Phenomenex Luna 5-µm C18 (2)-250 x 4.6-mm, 5-µm) as a stationary phase, flow rate of 1.0 mL/min with detection at 270 nm. The RRF for Zidovudine related impurity C, Lamivudine salicylic acid and Zidovudine related impurity B were 2.07, 0.13 and 1.28 respectively.   Results obtained for quantification of the related substance in lamivudine and zidovudine single dose oral solid dosage form using the RRF and know standards shows no significant difference at 95 % confidence interval. The RRF can therefore be used for the quantification of know related impurities in lamivudine zidovudine oral dosage form using the stated chromatographic conditions

A qualitative study of Telehealth patient information leaflets (TILs) : are we giving patients enough information?

BACKGROUND: The provision of patient information leaflets regarding telehealth has been perceived by potential consumers as a strategy to promote awareness and adoption of telehealth services. However, such leaflets need to be designed carefully if adoption and awareness among potential users is to be promoted. Therefore, the aims of this study were: first, to see how telehealth was portrayed in some of the existing telehealth leaflets (THLs). Second, to explore patients' perceptions of the existing THLs and their engagement with the concept and how THLs can be optimised. METHODS: A two-step approach was employed to address the aims of this study. The first phase involved the use of discourse analysis to compare 12 electronically and publically available THLs, with the existing THL guidance "Involve Yorkshire and Humber". The second phase involved conducting 14 semi-structured interviews with potential telehealth users/patients to gauge their perception and engagement with the concept, using the two leaflets that were mostly matching with the guidance used. Six interviews were audio-recorded and eight had detailed jotted notes. The interviews were transcribed and thematically analysed to identify key themes. RESULTS: The discourse analysis showed certain gaps and variations within the screened leaflets when addressing the following aspects: cost of the telehealth service, confidentiality, patients' choices in addition to equipment use and technical support. Analysis of the interviews revealed patients' need for having clear and sufficient information about the telehealth service within the THLs; in addition to, patients' preference for the use of simpler terminologies for telehealth description and the provision of clear simple texts with pictorial presentations. The interviews also revealed certain limitations against adoption of telehealth by the participants, such as: lack of privacy and confidentiality of information, fear of technology breakdown and equipment failure, loss of face-to-face contact with healthcare professionals and being too dependent on the telehealth service. CONCLUSION: The current study showed a great variation among the screened THLs and highlighted certain gaps within the content and presentation of these leaflets. However, the study also highlighted certain key issues to be considered when designing THLs in the future to enhance telehealth uptake and use by patients

Comparing changes in haematologic parameters occurring in patients included in randomized controlled trials of artesunate-amodiaquine vs single and combination treatments of uncomplicated falciparum in sub-Saharan Africa

<p>Abstract</p> <p>Background</p> <p>Artesunate-amodiaquine (AS&AQ) is a widely used artemisinin combination therapy (ACT) for falciparum malaria. A comprehensive appreciation of its effects on haematology <it>vs </it>other anti-malarials is needed in view of potential safety liabilities.</p> <p>Methods</p> <p>Individual-patient data analysis conducted on a database from seven randomized controlled trials conducted in sub-Saharan African comparing AS&AQ to reference treatments in uncomplicated falciparum malaria patients of all ages. Haematologic values (white cells total and neutrophil counts, haemoglobin/haematocrit, platelets) were analysed as both continuous and categorical variables for their occurrence, (severity grade 1-4) and changes during follow-up. Risks and trends were calculated using multivariate logistic random effect models.</p> <p>Results</p> <p>4,502 patients (72% < 5 years old), from 13 sites in nine countries with 28-day follow-up were treated with AS&AQ (45%) or a comparator (other forms of ACT accounted for 27%, other combination 12%, mono-therapies 16%). Pre-treatment leucopaenia (3%) and neutropaenia (6%) were infrequent; anaemia was common (39%). The treatment-emergent adverse events incidence (TEAE = condition not present or less severe pre-treatment) was 11% for neutropaenia, 6% for thrombocytopaenia with AS&AQ and not different from treatment groups; anaemia was higher with AS&AQ (20%) or other forms of ACT (22%) than in non-artemisinin groups (4%, <it>p </it>= 0.001). Multivariate analysis showed that the risk of anaemia, thrombocytopaenia, and leucopaenia decreased with follow-up time, while neutropaenia increased; the risk of anaemia and thrombocytopaenia increased with higher baseline parasitaemia and parasitological reappearance. White cells total count was not a good surrogate for neutropaenia. No systematic significant difference between treatments was detected. Older patients were at lower risks.</p> <p>Conclusion</p> <p>The effects of AS&AQ on haematologic parameters were not different from those of other anti-malarial treatments used in sub-Saharan Africa. This analysis provides the basis for a broader evaluation of haematology following anti-malarial treatment. Continuing monitoring of haematologic safety on larger databases is required.</p

Co-infection by human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia virus type 1 (HTLV-1): does immune activation lead to a faster progression to AIDS?

<p>Abstract</p> <p>Background</p> <p>Recent data have shown that HTLV-1 is prevalent among HIV positive patients in Mozambique, although the impact of HTLV-1 infection on HIV disease progression remains controversial. Our aim was to determine the phenotypic profile of T lymphocytes subsets among Mozambican patients co-infected by HIV and HTLV-1.</p> <p>Methods</p> <p>We enrolled 29 patients co-infected by HTLV-1 and HIV (co-infected), 59 patients mono-infected by HIV (HIV) and 16 healthy controls (HC), respectively.</p> <p>For phenotypic analysis, cells were stained with the following fluorochrome-labeled anti-human monoclonal antibodies CD4-APC, CD8-PerCP, CD25-PE, CD62L-FITC, CD45RA-FITC. CD45RO-PE, CD38-PE; being analysed by four-colour flow cytometry.</p> <p>Results</p> <p>We initially found that CD4⁺T cell counts were significantly higher in co-infected, as compared to HIV groups. Moreover, CD4⁺T Lymphocytes from co-infected patients presented significantly higher levels of CD45RO and CD25, but lower levels of CD45RA and CD62L, strongly indicating that CD4⁺T cells are more activated under HTLV-1 plus HIV co-infection.</p> <p>Conclusion</p> <p>Our data indicate that HTLV-1/HIV co-infected patients progress with higher CD4⁺T cell counts and higher levels of activation markers. In this context, it is conceivable that in co-infected individuals, these higher levels of activation may account for a faster progression to AIDS.</p