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Introduction: CEP-37440 was synthesized and supplied by the research and development division of Teva Branded Pharmaceutical Products (West Chester, PA, United States). CEP-37440 represents a newly developed compound that exhibits selectivity inhibition of Focal Adhesion Kinase and Anaplastic Lymphoma Kinase FAK/ALK receptors, demonstrating novel characteristics as an orally active inhibitor. The simultaneous inhibition of ALK and FAK can effectively address resistance and enhance the therapeutic efficacy against tumors through a synergistic mechanism. Methods: The objective of this research was to create an LC-MS/MS method that is precise, efficient, environmentally friendly, and possesses a high level of sensitivity for the quantification of CEP-37440 in human liver microsomes (HLMs). The aforementioned approach was subsequently employed to evaluate the metabolic stability of CEP-37440 in HLMs in an in vitro setting. The validation procedures for the LC-MS/MS analytical method in the HLMs were performed following the bio-analytical method validation guidelines set out by the US-FDA. The AGREE program was utilized to assess the ecological impacts of the current LC-MS/MS methodology. Results and Discussion: The calibration curve linearity was seen in the range of 1-3000 ng/mL. The inter-day accuracy (% RE) exhibited a range of -2.33% to 3.22%, whilst the intra-day accuracy demonstrated a range of -4.33% to 1.39%. The inter-day precision (% RSD) exhibited a range of 0.38% to 3.60%, whilst the intra-day precision demonstrated a range of 0.16% to 6.28%. The determination of the in vitro half-life (t1/2) and moderate intrinsic clearance (Clint) of CEP-37440 yielded values of 23.24 min and 34.74 mL/min/kg, respectively. The current manuscript is considered the first analytical study for CEP-37440 quantification with the application to metabolic stability assessment. These results suggest that CEP-37440 can be categorized as a pharmaceutical agent with a moderate extraction ratio. Consequently, it is postulated that the administration of CEP37440 to patients may not lead to the accrual of dosages within the human organs. According to in silico P450 metabolic and DEREK software, minor structural alterations to the ethanolamine moiety or substitution of the group in drug design have the potential to enhance the metabolic stability and safety profile of novel derivatives in comparison to CEP-37440. [ABSTRACT FROM AUTHOR]

Polyvinyl chloride (PVC) membrane sensors were constructed and developed for the determination of procainamide HCl (PR). Three membrane sensors incorporating α-, β- and γ- cyclodextrin (CD) as ionophores with potassium tetrakis (4-chlorophenyl) borate (KTpClPB) as the ion additive, o-nitro phenyl ether (o-NPOE) as the plasticizer and a PVC matrix. The reaction mechanisms were based on inclusion complexes. The developed α- and β- CD sensors exhibited near-Nernstian profile, whereas γ- CD showed a non-Nernstian response. At pH 4 -8, the sensors exhibited a calibration range for PR of 10-3 to 10−6, and the detection limits were 2.40 × 10-6, 2.12 × 10-6, 2.40 × 10-6 for α-, β- and γ- CD sensors, respectively. Interference was investigated by studying the selectivity coefficient values of the test sensors, which indicated that the methods were free from interference from investigated species. The determination of PR exhibited high recovery and favorable relative standard deviation using the investigated sensors. The sensors were subsequently used for the quantification of PR in a pharmaceutical formulation and the potentiometric results agreed with those of a spectrophotometric method. A molecular docking (MD) study was used to predict the structure of the inclusion complexes of PR (guest) and α- or β- or γ-CD (host). The study results indicated that the formed complexes were stable with sufficient binding energy.

The unique properties of calcium oxide (CaO) and zinc oxide (ZnO) at the nanoscale have attracted the interest of scientists as promising electrically conductive substances for sensing purposes. The content of terbinafine hydrochloride (TRF) in pharmaceutical tablets was determined using a novel coated, wire‐functionalized CaO/ZnO nanocomposite membrane sensor biogenically produced from Lavandula spica extract. Sodium tetraphenylborate was used to prepare the active material (TRF‐TBP). The newly modified sensor gave excellent potentiometric sensitivity with the least squares regression equation EmV=(−58.88X±0.3)+log [TRF]+549.78 and covered a wide linear range (5.0×10−9–1.0×10−2 mol/L) of TRF samples. In contrast, the standard TRF‐TBP sensor wasn't as sensitive when (2.5×10−6–1.0×10−2 mol/L). TRF solutions with regression equation of (−55.728X±0.7)+log [TRF]+396.64. The appropriate pH range was 3–6. The principles of analytical methodology were applied to investigate the validity and suitability of the proposed technique. The proposed sensors were found to be suitable and efficient for the detection of TRF on tablets. [ABSTRACT FROM AUTHOR]

A new, selective and sensitive HPLC method for the determination of lixivaptan, an oral selective vasopressin 2 (V2)-receptor antagonist, was investigated and validated. A Waters symmetry C18 column was used as a stationary phase in isocratic elution mode using a mobile phase composed of KH2PO4 (100 mM)-acetonitrile (40: 60, v/v) at a flow rate of 1.5 mL min-1. Diclofenac was used as the internal standard (IS). Lixivaptan and the IS were extracted from plasma by protein precipitation and were detected at 260 nm. Lixivaptan and diclofenac were eluted at 3.6 and 6.2 min, respectively. The developed method showed good linearity over the calibration range of 50 -1000 ng mL-1 with a lower limit of detection of 16.5 ng mL-1. The extraction percentage of lixivaptan in the mouse plasma was in the range of 88.88 - 114.43%, which indicates acceptable extraction. The aforementioned method was validated according to guidelines of the International Council on Harmonization (ICH). The intra- and inter-day coefficients of variation did not exceed 5.5%. This method was presented to be simple, sensitive, and accurate and was successfully adapted in a pharmacokinetic study of the profile of lixivaptan in mouse plasma. A mean maximum plasma concentration of lixivaptan of 113.82 ng mL-1 was achieved in 0.5 h after oral administration of a 10 mg kg-1 dose in mouse as determined using the developed method.

The fabrication and development of two polyvinyl chloride (PVC) membrane sensors for assaying phenobarbitone sodium are described. Sensors 1 and 2 were fabricated utilizing β- or γ-cyclodextrin as ionophore in the presence of tridodecylmethylammonium chloride as a membrane additive, and PVC and dioctyl phthalate as plasticizer. The analytical parameters of both sensors were evaluated according to the IUPAC guidelines. The proposed sensors showed rapid, stable anionic response (-59.1 and -62.0 mV per decade) over a relatively wide phenobarbitone concentration range (5.0 × 10-6-1 × 10-2 and 8 × 10-6-1 × 10-2 mol L-1) in the pH range of 9-11. The limit of detection was 3.5 × 10-6 and 7.0 × 10-6 mol L-1 for sensors 1 and 2, respectively. The fabricated sensors showed high selectivity for phenobarbitone over the investigated foreign species. An average recovery of 2.54 μg mL-1 phenobarbitone sodium was 97.4 and 101.1 %, while the mean relative standard deviation was 3.0 and 2.1 %, for sensors 1 and 2, respectively. The results acquired for determination of phenobarbitone in its dosage forms utilizing the proposed sensors are in good agreement with those obtained by the British Pharmacopoeial method.

C17H21ClN2S, orthorhombic, Pbca (no. 61), a = 17.2134(6) Å, b = 8.2251(2) Å, c = 22.5220(7) Å, V = 3188.71(17) Å3, Z = 8, Rgt(F) = 0.0371, wRref(F2) = 0.0933, T = 100 K.