Bioanalytical Method Development And Validation Of Ibrutinib In Biological Matrices By Lc-Ms/Ms

Objective: The main aim of the research was to develop a fast and highly sensitive bioanalytical LC-MS/MS technique for the quantitation of ibrutinib in human plasma. Methods: Chromatography has achieved on a reverse phase-symmetry C18 (75 mm × 4.6 mm, 3.5 µm) column with gradient elution by acetonitrile, methanol and 0.1%v/v formic acid as the mobile phase. Chromatographic peaks were resolved with 0.7 ml/min flow rate. Drug was extracted with ethyl acetate solvent by liquid-liquid extraction method. Monitoring of transition of m/z 441.2 and 55.01 for ibrutinib and 446.5 and 60.01 for Ibrutinib-D5 were made on multiple reaction monitoring. Results: Calibration curve of ibrutinib was linear over 1-600 ng/ml concentration range with a regression coefficient (r2) value of>0.99. The % RSD values were less than 8.5% for inter-day and intra-day precision and accuracy. The method has excellent recovery and the percentage recovery values of lower quality control (LQC), median quality control (MQC) and higher quality control (HQC) samples were 101.86%, 102.8%, and 99.28% respectively. Conclusion: The drug was stable for more time at variable stability conditions and method was successfully applicable to the regular analysis of ibrutinib in biological matrices.

Detection of Pasteurella multocida in experimentally infected embryonated chicken eggs by PCR assay.

Applicability of polymerase chain reaction (PCR) assay to detect Pasteurella multocida in experimentally infected embryonated chicken egg was assessed in the present study. PCR assay rapidly and specifically detected the genome of P. multocida in amniotic fluid, allantoic fluid and homogenates of infected embryo and its membranes. The sensitivity of detection was as low as 20 bacterial cells/ml of allantoic or amniotic fluids. Detection of P. multocida in dead embryos by PCR was possible up to 6 and 30 days or more following storage of dead embryos at 37 degrees C, and at 4 degrees C as well as at -20 degrees C, respectively. The study revealed that PCR assays could be employed directly for detection and confirmation of P. multocida infection in experimentally infected chicken embryos.

Cost and efficiency of HIV voluntary counselling and testing centres in Andhra Pradesh, India.

BACKGROUND: [corrected] As part of the effort to control HIV/AIDS, the number of HlV voluntarycounselling and testingcentres (VCTCs) is increasing rapidly in the public health system of the Indian state of Andhra Pradesh, which is estimated to have one of the highest rates of HIV infection in India. However, systematic data on the cost and efficiency of providing VCT services in India are not available to help guide efficient use of resources for these services. METHODS: We used standardized methods to obtain detailed cost and output data for the 2002-03 fiscal year from written records and interviews in 17 VCTCs in the public health system in Andhra Pradesh. We calculated the economic cost per client receiving VCT services, and analysed the variation and determinants of total and unit costs across VCTCs. We used multivariate regression techniques to estimate incremental unit costs. We assessed hurdles towards serving an optimal number of clients by VCTCs. RESULTS: In the 2002-03 fiscal year, 32 413 clients received the complete sequence of services at the 17 VCTCs, including post-HIV test counselling. The number of clients served by each VCTC ranged from 334 to 7802 (median 979). The overall HIV-positive rate in post-test counselled clients was 20.5% (range 5.4%-52.6%). The cost per client for the complete VCT sequence varied 6-fold between VCTCs (range Rs 141.5-829.6 [US 2.92-17.14 dollars], median Rs 363.5 [US 7.51 dollars]). The cost per client was significantly lower at VCTCs with more clients (p < 0.001, R2 = 0.83; power function) due to substantial fixed costs. Personnel made up the largest component of cost (53.7%). The cost per client had a significant direct relation with percent personnel cost for VCTCs (p < 0.001, R2 = 0.58; exponential function). A multiple regression model revealed that the incremental cost of providing complete VCT services to each HIV-positive and -negative client was Rs 123.5 (US 2.54 dollars) and Rs 59.2 (US 1.22 dollars), respectively. Fourteen VCTCs (82.4%) reported that they could serve more clients with the available personnel and infrastructure, and that inadequate demand for their services was the main hurdle towards achieving this. CONCLUSION: These data suggest that the efforts of the National AIDS Control Organisation of India and the Andhra Pradesh State AIDS Control Society in increasing VCTCs could yield even higher benefit if the demand for these services was enhanced, as this would increase the number of clients served and reduce the cost per client. Ongoing systematic cost-efficiency analysis is necessary to help guide efficient use of HIV-control resources in India.

Ocular and systemic lesions in children with HIV.

The spectrum of ocular lesions in children with HIV infection is different from that seen in adults. Ocular lesions in pediatric AIDS patients have not been studied in India. We analyzed the clinical profile, demographic characteristics, ocular and systemic lesions in children with AIDS seen in a referral eye institute in India. The clinical profile and demographic features were studied and complete ocular examination was done. Systemic findings were evaluated at an AIDS care center and recorded in a precoded proforma. Out of the 218 cases of HIV infection seen at our hospital between December 1993 and October 1999, 12 (5.50%) were below 15 years of age. Seven (58.33%) were males and 5 (41.66%) were females with the mean age of 6.5 years and median age of 6.2 years. Vertical transmission was the most common mode of infection (58.33%). Seven (58.33%) of these patients had systemic infection, the most common being pulmonary tuberculosis (42.85%). Ocular lesions were found in 6 (50%) patients. The most common ocular lesions were anterior uveitis and cytomegalovirus retinitis (CMV) (33%) followed by retinal detachment (16.66%) and vitreous hemorrhage (16.66%). High prevalence of ocular lesions in pediatric AIDS patients in India in a referral eye centre was observed. The most common lesions were anterior uveitis followed by CMV retinitis. The management in such cases was often challenging in a developing country like India.

Artificial intelligence for medical decision making.

Artificial intelligence techniques find extensive applications in medical decision making and other aspects of health care. A number of successful expert systems have been developed in various disciplines of medicine. This paper gives an overview of expert system techniques, describes some practical systems, and discusses the relevance of such systems in clinical diagnosis and management of diseases.