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This study aimed to describe the use of liquid crystal display (LCD) three-dimensional (3D) printing technology to prepare moulds for vortioxetine hydrobromide (VOR) tablet placebos and provide an economical, convenient, and flexible method for the small-batch preparation of special-shaped, scored, and coated placebo tablets. First, LCD 3D printing was used to generate different placebo moulds of VOR tablets based on VOR tablet digital models subtracted from the digital models of cuboid moulds by Boolean operation to optimise the structures of moulds. The better placebo mould had a parting surface located at the 7/10 height of the packing cavities and the positioning columns and slots were three pairs, and the efflux space had slender efflux channels combined with wide efflux tanks. Next, the placebo mould was corrected by the dimensional compensation method due to the shrinkage rates of the packing cavities (2.42%) and placebo prescription (1.12%) and the thickness of the film coating (25.08 μm). The placebo prescription was 8% hydroxypropyl methylcellulose (SH K15M) hydroalcoholic gel, and its mass ratio to lactose was 0.8:2. The placebos were coated with 13% gastric-soluble film coating solution for 30 min and polished with the 30% PEG 4000 solution. The National Bureau of Standards value between the VOR tablets and their placebos was 1.22 ± 0.10 (less than1.5). Finally, the mass of the placebos was similar to that of the VOR tablets. Their dimensional differences were less than 0.1 mm. Their mass, colour, odour, shape, and texture were all similar, which were assessed by manual evaluation. In conclusion, the preparations of VOR tablet placebos can be applied in placebo-controlled trials, and LCD 3D printing has an extensive application value in preparing placebo tablets., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2022. Published by Elsevier B.V.)

This study aimed to prepare effervescent tablets of traditional Chinese medicine Xianganfang with fresh juice using a semi-solid 3D printer with three cartridge holders to seperate acid and alkali source by drug paste through model design to avoid sticking impact and premature effervescence during the tableting in the conventional preparation process. The powder of Xianganfang including fresh juice of Phyllanthus emblica and licorice extract was obtained by vacuum freeze-drying with 50% mannitol as cryoprotectant. Then, the formulation of 3D-printed effervescent tablets was investigated. Further 5% HPMC hydroalcoholic gel was mixed with sodium bicarbonate and freeze-dried Xianganfang powder to prepare alkali source and drug paste respectively while 30% PVP ethanol solution was mixed with tartaric acid to prepare acid source paste; these three pastes had good printability. The pastes of drug, acid, and alkali were loaded into three syringe cartridges separately and numbered as "3," "5," and "7," according to cartridge holders of the 3D printer, and printed in the order of "537,353,735" for separating acid and alkali by drug to avoid premature effervescence. And the basic printing parameters were optimized. The tablets were evaluated by the appearance, tablet weight variation, hardness, disintegration time, friability, pH, and stability. The physicochemical properties all conformed to the Chinese Pharmacopoeia 2020 edition. The content of the active ingredient gallic acid was 0.769 ± 0.019 mg/g. This study provided a new method to prepare effervescent tablets of traditional Chinese medicine with fresh juice using 3D printing technology., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Emerging epidemiological researches have been performed to assess the association of ESR1 PvuII (rs2234693 T>C) polymorphism with the risk of cancer, yet with conflicting conclusions. Therefore, this updated meta-analysis was performed to make a more accurate evaluation of such relationship. We adopted EMBASE, PubMed, CNKI, and WANFANG database to search relevant literature before January 2018. Odds ratios (ORs) and 95% confidence intervals (CIs) were employed to estimate the relationship strengths. In final, 80 studies (69 publications) involving 26428 cases and 43381 controls were enrolled. Our results failed to provide significant association between overall cancer risk and PvuII polymorphism under homozygous (TT vs. CC) and heterozygous (TT vs. CT) models. Statistically significant relationship was only observed for PvuII polymorphism in allele model T vs. C (OR=0.95, 95% CI=0.91-0.99). Stratification analysis by cancer type suggested that T genotype significantly decreased prostate cancer risk (TT vs. CC: OR=0.79, 95% CI=0.66-0.94; T vs. C: OR=0.89, 95% CI=0.82-0.98), Leiomyoma risk (T vs. C: OR=0.82, 95% CI=0.68-0.98), and HCC risk (TT vs. CC: OR=0.45, 95% CI=0.28-0.71; T vs. C: OR=0.67, 95% CI=0.47-0.95). Furthermore, significantly decreased risk was also found for Africans, population-based and hospital-based studies in the stratified analyses. These results suggest that ESR1 PvuII (rs2234693 T>C) polymorphism may only have little impact on cancer susceptibility. In the future, large-scale epidemical studies are warranted to verify these results., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Co-administration of opioids with benzodiazepines is very common around the world. A semi-automated method was developed for the determination of four opioids and two benzodiazepines as well as their metabolites (including glucuronide metabolites) in human urine, based on on-line column-switching-solid-phase extraction (CS-SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The CS-SPE was performed by loading 200μL of urine sample to an Oasis HLB cartridge. Detection was achieved using a LC-MS/MS system equipped with an electrospray ionization source (ESI). For unequivocal identification and confirmation, two selected reaction monitoring transitions were registered for each compound, and no co-elution of interferences was observed at the expected retention time. Significant ion suppressions were observed for most analytes during chromatographic runs, but isotope-labeled internal standards (ISs) were used and found to be useful to compensate for the determination error caused by the matrix effect. The assay's linearity ranged from 1-20ng/mL to 800-1000ng/mL for 23 compounds, except for lorazepam (LOR), whose linearity was in the range of 1-100ng/mL. This method showed to be precise and accurate. The relative standard deviation (RSD) % values of within-run precision, between-run precision and total precision were not greater than 10.4% (n=3), 12.9% (n=5) and 15.1% (n=15), respectively. Accuracy values were in the range of 87.5-110%. Limits of detection (LODs) ranged from 0.2ng/mL to 5ng/mL, and limits of quantification (LOQs) ranged from 1ng/mL to 20ng/mL. The method was applied to the assay of 12 samples from forensic cases, which exemplified the co-administration of benzodiazepines (BZDs) by some heroin abusers. This method was of high sensitivity, selectivity and reliability, minimum sample manipulation, semi-automation, and fairly high throughput (analysis time per sample was 20min). The method developed will be useful for the detection of co-administrated drugs and the study of the interactions of BDZs with opioids., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A novel method for the screening of 151 drugs of abuse and toxic compounds in human whole blood has been developed and validated by online solid-phase extraction with liquid chromatography coupled to time-of-flight mass spectrometry. Analytes were extracted and separated by using a fully automated online solid-phase extraction liquid chromatography system with total chromatographic run time of 26 min. Time-of-flight mass spectrometry screening of 151 drugs of abuse and toxic compounds was performed in a full-scan (m/z 50-800) mode using an MS(E) acquisition of molecular ions and fragment ions data at two collision energies (one was 6 eV and another one was in the range of 5-45 eV). The compounds were identified based on retention times and exact mass of molecular ions and fragment ions. The limit of detection ranged from 1 to 100 ng/mL and the recovery of the method ranged from 6.3 to 163.5%. This method is proved to be a valuable screening method allowing fast and specific identification of drugs in human whole blood., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A μElution solid-phase extraction (SPE) liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of diazepam, nordiazepam, oxazepam, oxazepam glucuronide, temazepam and temazepam glucuronide in human whole blood is presented. 200 μL of whole blood samples were loaded onto a Waters Oasis HLB 96-well μElution SPE plate using 75 μL of methanol as the elution solvent, and the eluents were injected into an Eclipse XDB C18 column. No hydrolysis, solvent transfer, evaporation or reconstitution was involved in the sample preparation procedures. Tandem mass spectrometric detection with Turbo Ion Spray was conducted via multiple reaction monitoring (MRM) under positive ionization mode. The method was validated and proved to be accurate (accuracy within 93-108%), precise (intra-day RSD<9.9% and inter-day RSD<7.2%) and sensitive with limits of detection (LOD) in the range of 0.05-0.25 ng/mL for all the compounds. Extraction recoveries were in the range of 31-80% for all the analytes. This method demonstrated to be reproducible and reliable. The applicability of the method was demonstrated by analysis of several forensic cases involving diazepam and its metabolites., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Ecgonine is suggested to be a promising marker of cocaine (COC) ingestion. A combined mass spectrometry (MS) and tandem MS (MS/MS) method was developed to simultaneously determine ecgonine and seven other metabolites of cocaine in human urine and whole blood with ultra-high-pressure liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The compounds were extracted from as little as 100 μL of sample by solid-phase extraction with a 96-well μElution solid-phase extraction plate. The protonated molecules or fragment ions at accurate mass acquired in MS mode were used to quantify specific analytes, following by dedicated MS/MS identification. The assay was linear in the range from 5 to 50-100 ng/mL for urine samples, except for ecgonine methyl ester (10-200 ng/mL) and ecgonine (40-400 ng/mL), and was linear from 1-2 to 50 ng/mL for whole blood samples, except for ecgonine methyl ester (20-1,000 ng/mL) and ecgonine (40-2,000 ng/mL). The correlation coefficients were all greater than 0.99. The limits of detection ranged from 0.2 to 16 ng/mL, and the lower limits of quantification ranged from 1 to 40 ng/mL. The repeatability and intermediate precision were 18.1% or less. The accuracy was in the range from 80.0 to 122.9%, process efficiencies were in the range from 8.6 to 177.4%, matrix effects were in the range from 28.7 to 171.0%, and extraction recoveries were in the range from 41.0 to 114.3%, except for ecgonine (12.8% and 9.3% at low and high concentrations, respectively). This method was highly sensitive in comparison with previously published methods. The validated method was successfully applied to the analysis of real samples derived from forensic cases, and the results verified that, on the basis of data from four positive samples, ecgonine is a promising marker of cocaine ingestion.