Guidelines for accurate application of green and white analytical concepts: Merits Versus demerits with insights of significant milestones of assessment tools applied for antiviral drugs

Microchemical Journal, Год журнала: 2024, Номер 199, С. 109917 - 109917

Опубликована: Янв. 10, 2024

Язык: Английский

---

A microcrystalline cellulose/metal-organic framework hybrid for enhanced ritonavir dispersive solid phase microextraction from human plasma

Carbohydrate Polymer Technologies and Applications, Год журнала: 2024, Номер 7, С. 100453 - 100453

Опубликована: Фев. 4, 2024

A hybrid of microcrystalline cellulose (MCC) with metal organic frame (MOF) was developed as an efficient adsorbent for dispersive solid phase microextraction (dSPME) ritonavir from spiked human plasma. The sorbent characterized by a high-resolution scanning electron microscope (HR-SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). MCC immersed in solution CaCl2, stirred soda water 1,3,5-benzenetricarboxylic acid, resulting white MCC/MOF composites, which were separated, washed, dried. hybrids examined under the HR-SEM showed morphological features different form Ca-1,3,5-benzenetricarboxylic acid (Ca-BTC) MOF. patterns Ca-BTC/MCC composites clearly displayed characteristic Ca-BTC MOF bands, indicating that successfully incorporated formation crystalline hybrids. FTIR spectra exhibited bands MCC, well MOFs. prepared applied dSPME plasma, before determination high performance liquid chromatography UV detection. After method optimization, best extraction efficiency achieved using 12.50 mg 250 µL acetonitrile eluent. This novel (Ca-BTC/MCC) merges advantages surface areas MOFs 820 m2 g−1 biodegradability sustainability MCC. Besides, higher compared unmodified To our knowledge, this work applies sorbents first time. These results open door to more applications these sample preparation biomedical analysis.

Язык: Английский

---

Simultaneous determination of nirmatrelvir, ritonavir, and beta-D-N4-hydroxycytidine in human plasma and epithelial lining fluid using LC-MS/MS and its clinical application to compare rates of achieving effective concentrations

Heliyon, Год журнала: 2025, Номер 11(2), С. e41737 - e41737

Опубликована: Янв. 1, 2025

Currently, the trials found that clinical efficacy of molnupiravir is lower than ritonavir-boosted nirmatrelvir. An explanation for these different efficacies in treatments still limited. The analysis method was developed and validated to simultaneously quantify nirmatrelvir, ritonavir, beta-D-N4-hydroxycytidine (NHC) human plasma bronchoalveolar lavage fluid (BALF) by electrospray ionization mass spectrometry. Our over a linear range 30-10000 ng/mL both matrices, with precision accuracy within 15 % across four concentrations. Recovery rates analytes from BALF were between 90.7-102.2 90.5-107.7 %, respectively. analytical then applied monitor therapeutic drug concentrations 59 samples 23 patients receiving nirmatrelvir or molnupiravir. By setting target 292 1205 NHC, based on vitro antiviral 90 virus inhibitory (EC90), drug's molecular weight its binding proteins, we observed had substantially greater achieving Additionally, monitored epithelial lining 4 NHC exhibited higher permeability lung tissue (approximately 20 nirmatrelvir). However, subtherapeutic also present fluid. These findings highlight importance considering factors determining drugs treating coronavirus disease 2019 (COVID-19).

Язык: Английский

---

Green adherent degradation kinetics study of Nirmatrelvir, an oral anti-COVID-19: characterization of degradation products using LC–MS with insilico toxicity profile

BMC Chemistry, Год журнала: 2023, Номер 17(1)

Опубликована: Март 17, 2023

The SARS-CoV-2 virus sets up a global catastrophe, and countries all around the world made significant efforts to halt spread. Nirmatrelvir (NMV) was lately approved by FDA as safe well-tolerated oral direct-acting antiviral medication for infection. Therefore, fast completely validated stability indicating method established-for first time- NMV determination. study used NaOH, HCl, neutral, H2O2, sunlight test under various stress conditions followed kinetics degradation investigation derivation of Arrhenius plot. analysis performed using Agilent Zorbax Eclipse-C18 column (5 µm, 4.6 × 250 mm) with mobile phase consisting acetonitrile: 50 mM ammonium acetate, pH = 5 (50:50, v/v, respectively) at flow rate 1.0 mL/min min run time. Diode array detector (DAD) set 225 nm quantify concentration range 5-500 µg/mL LOD LOQ 0.6 2 µg/mL, respectively. Method's greenness assessed different metrics including Analytical Eco-Scale, Greenness Assessment Procedure Index, GAPI, Greenness, AGREE. A thorough revealed that more susceptible alkaline hydrolysis compared acid hydrolysis. In contrast, it found remained stable when subjected oxidative, sun-induced conditions. Moreover, alkali-induced were follow pseudo order kinetics. Consequently, half lifetime studied room temperature calculated mechanism pathways circumstances proposed LC-MS-UV. Toxicities products ProTox-II, along parent NMV, shown be hardly hazardous.

Язык: Английский

---

Development of a novel quality by design–enabled stability‐indicating HPLC method and its validation for the quantification of nirmatrelvir in bulk and pharmaceutical dosage forms

Biomedical Chromatography, Год журнала: 2024, Номер 38(3)

Опубликована: Янв. 16, 2024

Abstract A systematic and novel quality by design–enabled, rapid, simple, economic stability–indicating HPLC method for quantifying nirmatrelvir (NMT) was successfully developed validated. An analytical target profile (ATP) established, critical attributes (CAAs) were allocated to meet the ATP requirements. The used chromatographic separation using a Purosphere column with 4.6 mm inner diameter × 250 (2.5 μm). analysis occurred at 50°C flow rate of 1.2 mL/min detection 220 nm. 10 μL sample injected, mobile phase consisted two components: A, containing 0.1% formic acid in water (20%), B, acetonitrile (80%). diluent prepared mixing 90:10 v/v ratio. retention time analyte determined be 2.78 min. Accuracy exceeded 99%, correlation coefficient greater than 0.999. validated characterized as precise, accurate, robust. Significantly, NMT found susceptible alkaline, acidic, peroxide conditions during forced degradation testing. stability‐indicating effectively separated products formed stress testing, underlining its effectiveness stability testing offering accuracy, reliability, sensitivity determining NMT.

Язык: Английский

---

Tailoring two white chromatographic platforms for simultaneous estimation of ritonavir-boosted nirmatrelvir in their novel pills: degradation, validation, and environmental impact studies

RSC Advances, Год журнала: 2023, Номер 13(38), С. 26719 - 26731

Опубликована: Янв. 1, 2023

As the COVID-19 pandemic is not yet over, Pfizer has launched novel pill Paxlovid® (Nirmatrelvir (NMV) co-packaged with ritonavir (RIT)) as an effective medication for hospitalized and non-hospitalized patients. Making pharmaceutical analysis greener more sustainable lately become main direction of research community. In this context, two fast, green, stability-indicating chromatographic methods were designed neat quantitative determination NMV RIT in their bulk dosage forms. Method I deemed first electro-driven attempt assay Paxlovid®. Herein, optimized conditions Micellar Electrokinetic Chromatographic (MEKC) method 50 mM borate buffer at pH 9.2 25 sodium lauryl sulfate (SDS) being used background electrolyte (BGE) on a deactivated fused silica capillary (50 cm length × μm id). II was isocratic reversed-phase HPLC separation using Zorbax-Eclipse C18 (4.6 250 mm, 5 particle size) column ammonium acetate acetonitrile mobile phase constituents flow rate 1 mL min-1. For sake simplicity increasing sensitivity, single wavelength 210 nm to both drugs. Linear correlations between peak areas concentration observed ranges 10-200 μg mL-1 5-100 methods. The impact versatile stress such hydrolysis, oxidation, photolysis stability studied. Fortunately, methodologies able separate drugs from degradants. Thus, indicating power proved. derived statistically validated agreement ICH guidelines. Furthermore, environmental friendliness sustainability these investigated compared cited holistic multicriteria evaluation tools namely Hexagon, AGREE, RGB12 metrics. Conclusively, proposed offered reliable, feasible, economic, white, alternatives

Язык: Английский

---

Population pharmacokinetic modeling and simulation for nirmatrelvir exposure assessment in Chinese older patients with COVID-19 infection

European Journal of Pharmaceutical Sciences, Год журнала: 2023, Номер 189, С. 106535 - 106535

Опубликована: Июль 23, 2023

Nirmatrelvir is an effective component of Paxlovid, the first oral antiviral drug granted emergency use authorization by FDA. prescribed extensively in older adult patients to treat coronavirus disease 2019 (COVID-19) infection. In this study, population pharmacokinetic modeling with clinical study data was employed explore profile nirmatrelvir Chinese COVID-19 The result suggests that can be described a one-compartment model first-order absorption and elimination population. calculated apparent clearance (CL/F), volumes distribution (V/F), rate constant (ka) for typical patient were 4.16 L/h, 39.1 L, 0.776, respectively. area under curve (AUC) approximately three-fold higher than AUCs Western young volunteers. At same doses, simulated increased 26%, 43%, 72%, 135% virtual populations creatinine clearances 60, 45, 30, 15 mL/min, Our research provides instructive reference dose selection adults.

Язык: Английский

---

Stability indicating RP-HPLC technique for simultaneous estimation of nirmatrelvir and ritonavir in their new copackaged dosage form for COVID-19 treatment

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 17, 2025

RP-HPLC technique was developed and optimized for simultaneous identification estimation of nirmatrelvir (NIR) ritonavir (RIT) in their new copackaged tablet. Stability studied after exposure to different five stress conditions; alkali, acid, heat, photo oxidation degradation. The chromatographic separation achieved using VDSpher PUR 100 ODS (4.6-mm x 15-mm), 3.5 μm column mixture 0.03 M potassium di-hydrogen phosphate buffer pH 4 acetonitrile (45:55, v/v) as mobile phase. temperature set at 40 °C, flow rate 1mL/min UV detection 215 nm. NIR RIT retention times were 3.94 ± 0.08 min 9.08 0.1 min, respectively. Linear relationship established range (1.5-105 µg/mL) (1-70 with good reproducibility. found mean percentage recoveries 100.03% 99.85%, method shows very sensitivity the LOQ LOD be 3.001 & 0.990 µg/mL, respectively 2.765 0.912 RIT. approach validated concerning ICH guidelines applied successfully dosage from. results assay proposed compared statistically by applying published one agreement.

Язык: Английский

---

Real-world Plasma Exposure of Nirmatrelvir/Ritonavir in Chinese Hospitalized Patients With COVID-19: A Multicenter Retrospective Study

Therapeutic Drug Monitoring, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Nirmatrelvir/ritonavir is licensed for the treatment of mild-to-moderate coronavirus disease (COVID-19) in patients at an increased risk progression to severe disease. However, data on real-world plasma exposure nirmatrelvir/ritonavir remain limited, particularly Chinese patients. This study aimed assess trough concentration (Ctrough) and identify its critical factors hospitalized treated with 300 mg/100 mg twice daily over a 5-day course. A high-performance liquid chromatography-tandem mass spectrometry assay was developed validated measure Ctrough. Correlation analyses were performed variables influencing Among 110 patients, 100% had concentrations above antiviral vitro 90% effective concentration. The median Ctrough nirmatrelvir 4.55 mcg/mL (15.6× concentration), ranging from 0.65 12.44 mcg/mL. Nirmatrelvir normal mild renal impairment cohorts comparable (4.09 ± 1.97 4.57 2.21 mcg/mL) but significantly moderate cohort (6.41 2.31 mcg/mL). Sex, age, obesity not associated exposure. high COVID-19, therapeutic drug monitoring should be routinely recommended, except impairment.

Язык: Английский

---

Comparison of greenness and blueness assessments for analytical methods used in the analysis of ritonavir, favipiravir, and molnupiravir: Applications in different matrices

Microchemical Journal, Год журнала: 2025, Номер unknown, С. 113165 - 113165

Опубликована: Фев. 1, 2025

Язык: Английский

---