scholarly journals Stability of extemporaneously prepared preservative-free methylphenidate 5 mg/mL intravenous solution

Author(s):  
Megan E Barra ◽  
Brian L Edlow ◽  
James T. Lund ◽  
Katherine S DeSanctis ◽  
John Vetrano ◽  
...  

Abstract Disclaimer In an effort to expedite the publication of articles , AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose To advance the implementation of consciousness-promoting therapies in patients with acute disorders of consciousness, the availability of potential therapeutic agents in formulations suitable for administration in hospitalized patients in the presence of complex comorbid conditions is paramount. The purpose of this study is to evaluate the long-term stability of extemporaneously prepared preservative-free methylphenidate hydrochloride (HCl) 5 mg/mL intravenous solution for experimental use. Methods A methylphenidate 5 mg/mL solution was prepared under proper aseptic techniques with Methylphenidate Hydrochloride, USP, powder mixed in sterile water for solution. Methylphenidate HCl 5 mg/mL solution was sterilized by filtration technique under USP <797>–compliant conditions. Samples were stored refrigerated (2-8°C) and analyzed at approximately days 1, 30, 60, 90, 180, and 365. At each time point, chemical and physical stability were evaluated by visual inspection, pH measurement, membrane filtration procedure, turbidometric or photometric technique, and high-performance liquid chromatography analysis. Results Over the 1-year study period, the samples retained 96.76% to 102.04% of the initial methylphenidate concentration. There was no significant change in the visual appearance, pH level, or particulate matter during the study period. The sterility of samples was maintained and endotoxin levels were undetectable throughout the 1-year stability period. Conclusion Extemporaneously prepared preservative-free methylphenidate 5 mg/mL intravenous solution was physically and chemically stable at 32, 61, 95, 186, and 365 days when stored in amber glass vials at refrigerated temperatures (2-8°C).

2020 ◽  
Author(s):  
Megan E. Barra ◽  
Brian L Edlow ◽  
James T. Lund ◽  
Katherine Sencion ◽  
John Vetrano ◽  
...  

Purpose: To advance the implementation of consciousness-promoting therapies in patients with acute disorders of consciousness, the availability of potential therapeutic agents in formulations suitable for administration in hospitalized patients in the presence of complex comorbid conditions is paramount. The purpose of this study is to evaluate the long-term stability of extemporaneously prepared preservative-free methylphenidate 5 mg/mL intravenous solution. Methods: A methylphenidate 5 mg/mL solution was prepared under proper aseptic techniques with Methylphenidate HCl USP powder mixed in sterile water for solution. Methylphenidate HCl 5 mg/ml solution was sterilized by filtration technique under USP <797> compliant conditions. Samples were stored refrigerated (2-8C) and analyzed at approximately day 1, 30, 60, 90, 180, and 365. At each time point, chemical and physical stability was evaluated by visual inspection, pH measurement, membrane filtration procedure, turbidometric or photometric technique, and high-performance liquid chromatography (HPLC) analysis. Results: Over the 1 year study period, the sample retained 96.76-102.04% of initial methylphenidate concentration. There was no significant change in the visual appearance, pH level or particulate matter during the study period. The sample maintained bacterial and fungi sterility, and endotoxin levels were undetectable throughout the 1 year stability period. Conclusions: Extemporaneously prepared preservative-free methylphenidate 5 mg/mL intravenous solution was physically and chemically stable for up to 365 days when stored in amber glass vials at refrigerated temperatures (2-8C).


Plants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1112
Author(s):  
Yan Yang ◽  
Liangfang Dai ◽  
Decai Wu ◽  
Limin Dong ◽  
Yisheng Tu ◽  
...  

Huperzia serrata is a traditional herb and endangered Chinese medicinal material, which has attracted much attention due to its production of Huperzine A (HupA). In vitro propagation of H. serrata is considered a new way to relieve the resource pressure of H. serrata. In this study, three different genotypic wild H. serrata were used for in vitro propagation. Then, the antioxidant activity and the content of HupA in the regenerated H. serrata were investigated. The results showed the survival rate of the explant was increased to 25.37% when using multiple sterilization processes. The best induction medium for H. serrata was the Schenk and Hildebrandt (SH) medium supplemented with 0.5 mg·L−1 Naphthalene acetic acid (NAA) and 0.1 mg·L−1 2,4-Dichlorophenoxyacetic acid (2,4-D), where the regeneration rate of the explant was to 57.04%. The best proliferation medium was the SH medium with NAA (1.0 mg·L−1), as the biomass of in vitro tissue increased 164.17 ± 0.41 times. High-performance liquid chromatography analysis showed that the in vitro culture of three genotypes could produce HupA and the content of HupA was 53.90–87.17 µg·g−1. The antioxidant experiment showed that the methanol extract of in vitro H. serrata had higher antioxidant activity than that of wild H. serrata. This study provides a reliable in vitro H. serrata culture protocol and laid an important foundation for the antioxidant capacity of the thallus and the content of HupA.


1997 ◽  
Vol 41 (3) ◽  
pp. 504-510 ◽  
Author(s):  
A Severin ◽  
E Severina ◽  
A Tomasz

Subinhibitory concentrations of clavulanate caused premature induction of stationary-phase autolysis, sensitization to lysozyme, and reductions in the MICs of deoxycholate and penicillin for Streptococcus pneumoniae. In the range of clavulanate concentrations producing these effects, this beta-lactam compound was selectively bound to PBP 3. Cell walls isolated from pneumococci grown in the presence of clavulanate showed increased sensitivity to the hydrolytic action of purified pneumococcal autolysin in vitro. High-performance liquid chromatography analysis of the peptidoglycan isolated from the clavulanate-grown cells showed major qualitative and quantitative changes in stem peptide composition, the most striking feature of which was the accumulation of peptide species carrying intact D-alanyl-D-alanine residues at the carboxy termini. The altered biological and biochemical properties of the clavulanate-grown pneumococci appear to be the consequences of suppressed D,D-carboxypeptidase activity.


Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2887
Author(s):  
Kena Li ◽  
Jens Prothmann ◽  
Margareta Sandahl ◽  
Sara Blomberg ◽  
Charlotta Turner ◽  
...  

Base-catalyzed depolymerization of black liquor retentate (BLR) from the kraft pulping process, followed by ultrafiltration, has been suggested as a means of obtaining low-molecular-weight (LMW) compounds. The chemical complexity of BLR, which consists of a mixture of softwood and hardwood lignin that has undergone several kinds of treatment, leads to a complex mixture of LMW compounds, making the separation of components for the formation of value-added chemicals more difficult. Identifying the phenolic compounds in the LMW fractions obtained under different depolymerization conditions is essential for the upgrading process. In this study, a state-of-the-art nontargeted analysis method using ultra-high-performance supercritical fluid chromatography coupled to high-resolution multiple-stage tandem mass spectrometry (UHPSFC/HRMSn) combined with a Kendrick mass defect-based classification model was applied to analyze the monomers and oligomers in the LMW fractions separated from BLR samples depolymerized at 170–210 °C. The most common phenolic compound types were dimers, followed by monomers. A second round of depolymerization yielded low amounts of monomers and dimers, while a high number of trimers were formed, thought to be the result of repolymerization.


2005 ◽  
Vol 95 (2) ◽  
pp. 158-165 ◽  
Author(s):  
A. Pegard ◽  
G. Brizzard ◽  
A. Fazari ◽  
O. Soucaze ◽  
P. Abad ◽  
...  

In the pepper Capsicum annuum CM334, which is used by breeders as a source of resistance to Phytophthora spp. and potyviruses, a resistance gene entirely suppresses reproduction of the root-knot nematode (Meloidogyne spp.). The current study compared the histological responses of this resistant line and a susceptible cultivar to infection with the three most damaging root-knot nematodes: M. arenaria, M. incognita, or M. javanica. Resistance of CM334 to root-knot nematodes was associated with unidentified factors that limited nematode penetration and with post-penetration biochemical responses, including the hypersensitive response, which apparently blocked nematode migration and thereby prevented juvenile development and reproduction. High-performance liquid chromatography analysis suggested that phenolic compounds, especially chlorogenic acid, may be involved in CM334 resistance. The response to infection in the resistant line varied with root-knot nematode species and was correlated with nematode behavior and pathogenicity in the susceptible cultivar: nematode species that quickly reached the vascular cylinder and initiated feeding sites in the susceptible cultivar were quickly recognized in CM334 and stopped in the epidermis or cortex. After comparing our data with those from other resistant pepper lines, we suggest that timing of the resistance response and the mechanism of resistance vary with plant genotype, resistance gene, and root-knot nematode species.


2006 ◽  
Vol 72 (6) ◽  
pp. 3924-3932 ◽  
Author(s):  
Erik Lys�e ◽  
Sonja S. Klemsdal ◽  
Karen R. Bone ◽  
Rasmus J. N. Frandsen ◽  
Thomas Johansen ◽  
...  

ABSTRACT Zearalenones are produced by several Fusarium species and can cause reproductive problems in animals. Some aurofusarin mutants of Fusarium pseudograminearum produce elevated levels of zearalenone (ZON), one of the estrogenic mycotoxins comprising the zearalenones. An analysis of transcripts from polyketide synthase genes identified in the Fusarium graminearum database was carried out for these mutants. PKS4 was the only gene with an enoyl reductase domain that had a higher level of transcription in the aurofusarin mutants than in the wild type. An Agrobacterium tumefaciens-mediated transformation protocol was used to replace the central part of the PKS4 gene with a hygB resistance gene through double homologous recombination in an F. graminearum strain producing a high level of ZON. PCR and Southern analysis of transformants were used to identify isolates with single insertional replacements of PKS4. High-performance liquid chromatography analysis showed that the PKS4 replacement mutant did not produce ZON. Thus, PKS4 encodes an enzyme required for the production of ZON in F. graminearum. Barley root infection studies revealed no alteration in the pathogenicity of the PKS4 mutant compared to the pathogenicity of the wild type. The expression of PKS13, which is located in the same cluster as PKS4, decreased dramatically in the mutant, while transcription of PKS4 was unchanged. This differential expression may indicate that ZON or its derivatives do not regulate expression of PKS4 and that the PKS4-encoded protein or its product stimulates expression of PKS13. Furthermore, both the lack of aurofusarin and ZON influenced the expression of other polyketide synthases, demonstrating that one polyketide can influence the expression of others.


2017 ◽  
Vol 35 (0) ◽  
Author(s):  
K. CECCHIN ◽  
A. FAVARETTO ◽  
S.M. SCHEFFER-BASSO ◽  
C.D. BERTOL ◽  
S.O. CHINI

ABSTRACT This study was conducted in order to verify if the phenological stage and the nitrogen fertilization interfere in the allelopathic activity and in the concentration of potentially allelopathic phenolic compounds of tough lovegrass (Eragrostis plana). The assay consisted of a bifactor 3 (0.100 and 200 kg N ha-1) x 2 (harvested in vegetative and reproductive stages), in a split plot design. The N doses constituted the main plot and the phenological stage during the harvest the subplots, resulting in six treatments. The tough lovegrass plants derived from each of the treatments were subjected to allelopathy bioassays, in which aqueous extracts of the aerial parts were applied to lettuce cypselae (Lactuca sativa) and to phytochemicals tests when ethanolic extracts were used, with subsequent partition with ethyl acetate, followed by a high-performance liquid chromatography analysis. There was nitrogen x phenological stage interaction on biological and chemical attributes. The allelopathic extracts were, in descending order of inhibition of germination, those from plants harvested at the vegetative stage and fertilized with 100 kg N and at the flowering stage with 200 kg N, which showed the highest catechin concentrations. The caffeic, ferulic, p-coumaric and vanillic acids were in a higher concentration in flowered and fertilized plants with 0 or 200 kg N. The management of the nitrogen fertilization and the harvesting age influence the allelopathic activity and the phytochemical composition of tough lovegrass.


2016 ◽  
Vol 82 (19) ◽  
pp. 5951-5959 ◽  
Author(s):  
Paul M. D'Agostino ◽  
Vivek S. Javalkote ◽  
Rabia Mazmouz ◽  
Russell Pickford ◽  
Pravin R. Puranik ◽  
...  

ABSTRACTThe mycosporine-like amino acids (MAAs) are a group of small molecules with a diverse ecological distribution among microorganisms. MAAs have a range of physiological functions, including protection against UV radiation, making them important from a biotechnological perspective. In the present study, we identified a putative MAA (mys) gene cluster in two New Zealand isolates ofScytonemacf.crispum(UCFS10 and UCFS15). Homology to “Anabaena-type”mysclusters suggested that this cluster was likely to be involved in shinorine biosynthesis. Surprisingly, high-performance liquid chromatography analysis ofS. cf.crispumcell extracts revealed a complex MAA profile, including shinorine, palythine-serine, and their hexose-bound variants. It was hypothesized that a short-chain dehydrogenase (UCFS15_00405) encoded by a gene adjacent to theS. cf.crispummyscluster was responsible for the conversion of shinorine to palythine-serine. Heterologous expression of MysABCE and UCFS15_00405 inEscherichia coliresulted in the exclusive production of the parent compound shinorine. Taken together, these results suggest that shinorine biosynthesis inS. cf.crispumproceeds via anAnabaena-type mechanism and that the genes responsible for the production of other MAA analogues, including palythine-serine and glycosylated analogues, may be located elsewhere in the genome.IMPORTANCERecently, New Zealand isolates ofS. cf.crispumwere linked to the production of paralytic shellfish toxins for the first time, but no other natural products from this species have been reported. Thus, the species was screened for important natural product biosynthesis. The mycosporine-like amino acids (MAAs) are among the strongest absorbers of UV radiation produced in nature. The identification of novel MAAs is important from a biotechnology perspective, as these molecules are able to be utilized as sunscreens. This study has identified two novel MAAs that have provided several new avenues of future research related to MAA genetics and biosynthesis. Further, we have revealed that the genetic basis of MAA biosynthesis may not be clustered on the genome. The identification of the genes responsible for MAA biosynthesis is vital for future genetic engineering.


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