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A simple, rapid and novel reverse phase-high performance liquid chromatography method was developed for quantification of molnupiravir in its capsule dosage form which is recently approved for phase III clinical trials in moderate coronavirus disease patients in India. The chromatographic separation of Molnupiravir was achieved on reverse phase-high performance liquid chromatography using Eclipse Plus C18 (150×4.6 mm, 5 µ) column with buffer (pH 4.5) and methanol (70:30 v/v) as mobile phase. Method was validated in accordance with recommendations of International Council for Harmonisation Q2 (R1) guidelines. The linearity of the method was found to be excellent over the concentration range of 49.80-149.40 µg/ml. The mean of the coefficient of determinations (r2, n=3) was found to be 0.9999. The precision values (percentage relative standard deviation) and overall percentage recovery was found to be acceptable. The proposed method effectively separated the drug from its degradation products. Hence, it can be used as a stabilityindicating assay method for the routine analysis of molnupiravir in pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

Background: The combination of whole-cell pertussis (wP) antigens with established diphtheria (D), tetanus (T), hepatitis B (HB), Haemophilus influenzae type b (Hib), and inactivated poliomyelitis (IPV) antigens provides a high-quality DTwP-IPV-HB-PRP∼T vaccine. This study evaluated a DTwP-IPV-HB-PRP∼T booster coadministered with measles, mumps, and rubella (MMR) vaccine., Methods: Phase II, open-label, randomized study. Healthy toddlers who had previously completed a DTwP-IPV-HB-PRP∼T or separate DTwP-HB-PRP∼T and IPV primary vaccination series received a DTwP-IPV-HB-PRP∼T booster vaccine at 12-24 months of age. All participants had also received 1 or 2 doses of measles-containing vaccine between primary vaccination and enrolment (N = 100 and N = 6, respectively). Those who had received 1 prior measles-containing vaccine received an MMR dose either concomitantly (N = 50) or 28 days after (N = 50) the DTwP-IPV-HB-PRP∼T booster. Immunogenicity was evaluated using validated assays and safety by parental reports., Results: Pre-booster vaccination, 100.0% participants showed antibody persistence after DTwP-IPV-HB-PRP∼T or DTwP-HB-PRP∼T and IPV for anti-T (≥0.01 IU/mL), anti-Hib (≥0.15 µg/mL), and anti-polio 3 (≥8 1/dil) and at least 95.8% of participants for anti-D (≥0.01 IU/mL), anti-HB (≥10 mIU/mL), and anti-polio 1 and 2 (≥8 1/dil). For the pertussis antigens, pre-booster antibody persistence (≥2 EU/mL) ranged from 88.6 to 88.7% (anti-PT), 91.4-98.6% (anti-FHA), 69.0-74.3% (anti-PRN), and 97.1-97.2% (anti-FIM). For the booster response, seroprotection based on either the primary series or measles-containing vaccination regimen was 100.0% for anti-D and anti-T (≥0.01 IU/mL and ≥0.10 IU/mL), anti-HB (≥10 mIU/mL and ≥100 mIU/mL), anti-Hib (≥0.15 µg/mL and ≥1 µg/mL) and anti-polio 1, 2, and 3 (≥8 1/dil), and for the pertussis antigens booster response ranged from 88.6 to 91.8% (anti-PT), 91.1-95.9% (anti-FHA), 88.6-93.9% (anti-PRN), and 95.9-98.6% (anti-FIM). There were no safety concerns in any group., Conclusions: This study showed good antibody persistence of the DTwP-IPV-HB-PRP∼T vaccine and good immunogenicity and safety of a booster dose given with MMR in the second year of life.Clinical Trials Registry India Number: CTRI/2018/04/013375., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: Multivalent vaccines containing whole-cell pertussis (wP) antigens combined with established diphtheria (D), tetanus (T), hepatitis B (HB), Haemophilus influenzae type b (Hib), and inactivated poliomyelitis (IPV) antigens allow the provision of a high-quality, affordable DTwP-IPV-HB-PRP∼T vaccine., Methods: Phase I/II, randomized, active-controlled, open-label study in healthy toddlers (Cohort I) and infants (Cohort II). Toddlers in Cohort I who had completed primary series D, T, P, HB, Hib, and polio vaccination received a booster dose of DTwP-IPV-HB-PRP∼T (N = 30) or DTwP-HB-PRP∼T + IPV (N = 15) vaccines at 15-18 months of age. After satisfactory review of safety data in Cohort I, infants in Cohort II received DTwP-IPV-HB-PRP∼T (N = 100) or DTwP-HB-PRP∼T + IPV (N = 50) at 6-8, 10-12, and 14-16 weeks of age. All infants in Cohort II had received previous oral polio and HB vaccines per country recommendations., Results: Booster and primary series vaccinations were well tolerated with no clinically significant differences between vaccine groups. Most adverse events were mild and resolved spontaneously; there were no vaccine-related serious adverse events and no deaths. In both vaccine groups, anti-D, anti-T, anti-HB, anti-Hib, and anti-polio 1, 2, and 3 seroprotection was 100% post-booster and post-primary series. For the pertussis antigens, booster response rate was > 86% in both groups. For the primary series, vaccine response rate was slightly higher for DTwP-IPV-HB-PRP∼T than DTwP-HB-PRP∼T + IPV for anti-PT (80.2% and 70.8%) and anti-FHA (81.3% and 68.8%), slightly lower for anti-PRN (72.5% and 81.3%), and similar in each group for anti-FIM (95.6% and 97.9%)., Conclusions: This study demonstrated a good safety and immunogenicity profile of the hexavalent DTwP-IPV-HB-PRP∼T vaccine for infant primary series vaccination at 6-8, 10-12, and 14-16 weeks of age and booster vaccination at 15-18 months of age and supported progression to the next development phase., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Clinical investigators involved in these studies (SP, MM, MDR, and APD) received fees from Sanofi Pasteur through their institutions for the conduct of these clinical studies, but did not receive any direct payment from Sanofi Pasteur in this regard. EJ, FN, and SM hold Sanofi stock. EJ, FN, and AM are employees of Sanofi Pasteur. DMP and EJ were employees of Sanofi Pasteur at the time of the study. BNP, SM, MVJ, SR, and SRJ are employees of Sanofi Healthcare India Private Ltd (SHIPL)., (© 2022 The Authors. Published by Elsevier Ltd.)