A novel liquid chromatography with quadrupole time-of-flight-tandem mass spectroscopy method for ultra-trace level identification and quantification of the genotoxic impurity 2,6-diamino-5-nitropyrimidin-4(3H)-one in valganciclovir hydrochloride.

In the present study, the main objective is to develop an analytical method for ultra-trace level measurement of 2,6-diamino-5-nitropyrimidin-4(3H)-one (DMNP) in valganciclovir hydrochloride (VAL) using liquid chromatography-quadrupole time-of-flight-tandem mass spectroscopy (LC-QTOF-MS/MS). In the early stages of guanine synthesis, DMNP is formed, and guanine is known to be the key starting material for the synthesis of VAL. Taking into consideration DMNP potential genotoxicity, this analytical method has been developed. This method is time saving and suitable for confirming the masses of parent and fragment ions by MS and MS/MS further fragmentation. An isocratic program and Acquity UPLC HSS cyano column (100 × 2.1 mm × 1.8 µm) were used to achieve optimal separation between VAL and the DMNP impurity. A 0.1% ammonia solution in Milli-Q water was used as mobile phase A, and methanol was used as mobile phase B in the ratio 90:10 v/v in isocratic mode. In accordance with the International Conference on Harmonization's requirements, the developed method was validated. The detection and quantification levels were found to be 0.028 and 0.083 ppm respectively. The DMNP impurity is linear from 0.083 to 1.245 ppm levels with correlation coefficient (R2 ) of 0.9960. The recoveries were found to be 97.0-107.9%.

Gender Differences in Health Related Quality of Life of People Living with HIV/AIDS in the Era of Highly Active Antiretroviral Therapy.

BACKGROUND: Data about the health-related quality of life (HR-QOL) of people living with HIV/AIDS (PLHA) after the implementation of free antiretroviral treatment in India are scarce. AIM: The study was to describe the HR-QOL and gender differences of PLHA in rural India. MATERIALS AND METHODS: Cross sectional study of 120 PLHA who came to the outpatient department in a rural district hospital. Assessment of the HR-QOL was performed through interviews using a validated structured questionnaire from the Medical Outcome Study HIV Health Survey. Linear regression with robust standard errors was used for multivariable analysis. RESULTS: Domains related to social and daily activities such as cognitive, role and social functioning had lower HR-QOL scores than domains related to physical health. Men had higher scores of HR-QOL in health transition, perceived HR-QOL, health distress, social functioning and role functioning. In multivariable analysis, factors associated with poorer HR-QOL were female sex, lower levels of education and being widowed or separated in women. CONCLUSIONS: HR-QOL of PLHA in rural India is poor, especially in widowed or separated women and people with lower levels of education. There is an urgent need of implementing programmes for improving the HR-QOL of HIV infected women in rural India.