Comparative study of six sequential spectrophotometric methods for quantification and separation of ribavirin, sofosbuvir and daclatasvir: An application on Laboratory prepared mixture, pharmaceutical preparations, spiked human urine, spiked human plasma, and dissolution test.

In accordance with International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines, six novel, simple and precise sequential spectrophotometric methods were developed and validated for the simultaneous analysis of Ribavirin (RIB), Sofosbuvir (SOF), and Daclatasvir (DAC) in their mixture without prior separation steps. These drugs are described as co-administered for treatment of Hepatitis C virus (HCV). HCV is the cause of hepatitis C and some cancers such as liver cancer (hepatocellular carcinoma) and lymphomas in humans. These techniques consisted of several sequential steps using zero, ratio and/or derivative spectra. DAC was first determined through direct spectrophotometry at 313.7 nm without any interference of the other two drugs while RIB and SOF can be determined after ratio subtraction through five methods; Ratio difference spectrophotometric method, successive derivative ratio method, constant center, isoabsorptive method at 238.8 nm, and mean centering of the ratio spectra (MCR) at 224 nm and 258 nm for RIB and SOF, respectively. The calibration curve is linear over the concentration ranges of (6-42), (10-70) and (4-16) µg/mL for RIB, SOF, and DAC, respectively. This method was successfully applied to commercial pharmaceutical preparation of the drugs, spiked human urine, and spiked human plasma. The above methods are very simple methods that were developed for the simultaneous determination of binary and ternary mixtures and so enhance signal-to-noise ratio. The method has been successfully applied to the simultaneous analysis of RIB, SOF, and DAC in laboratory prepared mixtures. The obtained results are statistically compared with those obtained by the official or reported methods, showing no significant difference with respect to accuracy and precision at p = 0.05.

Prediction of Fetal Hypertrophic Cardiomyopathy in Diabetic Pregnancies Compared with Postnatal Outcome.

OBJECTIVE: The aim of this study was to estimate the accuracy of prenatal assessment of interventricular septum (IVS) thickness, right myocardial wall thickness (RMWT), and left myocardial wall thickness (LMWT) by two-dimensional (2D) ultrasound for the prediction of perinatal mortality and postnatal diagnosis of hypertrophic cardiomyopathy (HCM) among diabetic pregnant women. SUBJECTS AND METHODS: A total of 120 diabetic pregnant women at 35 weeks or more were enrolled in this study from January 1, 2012, to June 30, 2014, at Ain Shams Maternity Hospital, Cairo, Egypt. The 2D ultrasound was done once for all the participants at the time of recruitment; IVS thickness, RMWT, and LMWT were measured. The glycosylated hemoglobin (HbA1c) levels of the participants were recorded. Neonatal assessment including postnatal echocardiography was done after 48 hours. Postnatal results were compared with the prenatal predictive results. RESULTS: Higher thickness values for IVS, RMW, and LMW were obtained in the uncontrolled diabetic cases (HbA1c > 6.5%) than in the controlled diabetic cases (HbA1c < 6.5%; P < 0.01). Of the included 120 neonates, 10 (8.3%) were stillborn, 99 (82.5%) had a five-minute Apgar score ≥7, and 4 (3.3%) had a five-minute Apgar score ≤3. The four neonates with severe neonatal distress died after admission to neonatal intensive care unit within one week after delivery. Out of 110 live-born neonates, 4 (3.6%) neonates had a low ejection fraction (EF) (<50%) due to HCM; of them 2 (1.8%) died within one week after delivery, while 2 (1.8%) survived. Another two (1.8%) neonates died from severe respiratory distress syndrome. A cutoff value of ≥4.5 mm for prenatal IVS thickness was predictive of neonatal distress due to HCM with a sensitivity of 82%, specificity of 68%, and diagnostic accuracy of 72%. A cutoff value of <1.18 for the ratio of IVS thickness to LMWT had a sensitivity of 82%, specificity of 72%, and diagnostic accuracy of 74% for the prediction of neonatal distress due to HCM. In this study, 8 of the 10 fetuses with intrauterine demise and the 2 neonates who died within one week after delivery due to heart failure had a prenatal IVS thickness of ≥4.5 mm, while 7 of the 10 fetuses with intrauterine demise and the 2 neonates who died postnatal from heart failure had a prenatal IVS thickness to LMWT ratio of ≤1.18. CONCLUSION: A prenatal IVS thickness of ≥4.5 mm or an IVS/LMWT ratio of ≤1.18 seems to be predictive of HCM and is associated with almost twofold higher risk of intrauterine fetal death and almost threefold higher risk of possibly relevant perinatal mortality.