Quality and stability of extemporaneous pyridoxal phosphate preparations used in the treatment of paediatric epilepsy

Mohamed-Ahmed, Abeer H. A.; Wilson, Matthew P.; Albuera, Maedelyn; Cui, Ting; Mills, Philippa B.; Footitt, Emma; Clayton, Peter T.; Tuleu, Catherine

doi:10.1111/jphp.12701

Cited by 15 publications

(38 citation statements)

References 29 publications

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“…From literature it is known that the use of highly aqueous mobile phases in reversed phase LC is beneficial for the retention of polar vitamins, such as the vitamers of B6 . So, columns mentioned under Section 2.2 were chosen in the light of their special characteristics that can help to retain polar compounds.…”

Section: Resultsmentioning

confidence: 99%

“…It consisted of a 0.1% solution of formic acid which is compatible with MS. This method is preferable to this suggested by Mohamed‐Ahmed since the latter contains trifluoroacetic acid which is known to suppress the MS signal .…”

Section: Resultsmentioning

confidence: 99%

“…In a few cases, these high doses caused impairment of the liver functions and even liver cirrhosis has been reported . As impurities of PLP are suspected to be responsible for toxic effects , it is of utmost importance to check the quality. This requires the availability of reliable analytical methods which are selective, sensitive, linear, precise and accurate.…”

Section: Introductionmentioning

confidence: 99%

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Development of a reversed phase liquid chromatographic method for analysis of pyridoxal‐5′‐phosphate and its impurities

et al. 2018

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Since no proper method is available in literature for the analysis of pyridoxal-5'-phosphate, a reversed phase liquid chromatographic method was developed and validated for specificity, sensitivity, linearity, precision and accuracy. Nine potential related substances and forced degradation products could be successfully separated from the main peak. The separation was achieved on a Polaris C18 column (250 × 4.6 mm i.d., 5 μm) using a mobile phase consisting of 20 mM ammonium formate in 0.65% formic acid - acetonitrile (98.8:1.2, v/v). Isocratic elution was performed at a flow rate of 1.0 mL/min and the analytes were detected by UV at 240 nm. The volatile mobile phase allowed also direct coupling to an ion-trap mass spectrometer with a positive electrospray ionization source to characterize unknown peaks in the chromatogram. The method can be used for quality control purposes as required by regulatory authorities to ensure the product's safety and efficacy.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Development of a reversed phase liquid chromatographic method for analysis of pyridoxal‐5′‐phosphate and its impurities

et al. 2018

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“…For the treatment of classical PNPO deficiency and PLPBP deficiency with insufficient stabilization on pyridoxine there is no pharmaceutical grade PLP available. Where PLP has been used for treatment in Europe and North America, it is a chemical compound or nutraceutical product where the PLP content may not be as stated . PLP, when in solution, may be rapidly degraded by light and/or oxygen with the formation of dimers or pyridoxic acid 5′‐phosphate and other products, respectively .…”

Section: B6 Vitamer Dose For the Treatment Of Plp‐deficiency And Vitamentioning

confidence: 99%

“…Where PLP has been used for treatment in Europe and North America, it is a chemical compound or nutraceutical product where the PLP content may not be as stated. 61 PLP, when in solution, may be rapidly degraded by light and/or oxygen with the formation of dimers or pyridoxic acid 5 0 -phosphate and other products, respectively. 61 Hence, when a liquid formulation is required each PLP dose should be prepared from a tablet or capsule and given without delay.…”

Section: Systemic Manifestationsmentioning

confidence: 99%

Disorders affecting vitamin B₆ metabolism

Wilson¹,

Plecko²,

Mills³

et al. 2019

J of Inher Metab Disea

172

193

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Vitamin B6 is present in our diet in many forms, however, only pyridoxal 5′‐phosphate (PLP) can function as a cofactor for enzymes. The intestine absorbs nonphosphorylated B6 vitamers, which are converted by specific enzymes to the active PLP form. The role of PLP is enabled by its reactive aldehyde group. Pathways reliant on PLP include amino acid and neurotransmitter metabolism, folate and 1‐carbon metabolism, protein and polyamine synthesis, carbohydrate and lipid metabolism, mitochondrial function and erythropoiesis. Besides the role of PLP as a cofactor B6 vitamers also play other cellular roles, for example, as antioxidants, modifying expression and action of steroid hormone receptors, affecting immune function, as chaperones and as an antagonist of Adenosine‐5'‐triphosphate (ATP) at P2 purinoceptors. Because of the vital role of PLP in neurotransmitter metabolism, particularly synthesis of the inhibitory transmitter γ‐aminobutyric acid, it is not surprising that various inborn errors leading to PLP deficiency manifest as B6‐responsive epilepsy, usually of early onset. This includes pyridox(am)ine phosphate oxidase deficiency (a disorder affecting PLP synthesis and recycling), disorders affecting PLP import into the brain (hypophosphatasia and glycosylphosphatidylinositol anchor synthesis defects), a disorder of an intracellular PLP‐binding protein (PLPBP, previously named PROSC) and disorders where metabolites accumulate that inactivate PLP, for example, ALDH7A1 deficiency and hyperprolinaemia type II. Patients with these disorders can show rapid control of seizures in response to either pyridoxine and/or PLP with a lifelong dependency on supraphysiological vitamin B6 supply. The clinical and biochemical features of disorders leading to B6‐responsive seizures and the treatment of these disorders are described in this review.

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Pyridoxine‐dependent epilepsy: Current perspectives and questions for future research

Coughlin

Gospe

2023

Annals of the Child Neurology Society

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Pyridoxine-dependent epilepsy (PDE) was historically defined by a dramatic clinical response to a trial of pyridoxine and the re-emergence of seizures after withdrawal of pyridoxine. Research conducted over the last seven decades has revealed that the phenotype of PDE results from multiple genetic disorders, and the most common disorder, PDE-ALDH7A1, is caused by a deficiency of an enzyme involved in lysine metabolism. PDE-ALDH7A1 is characterized by more than epilepsy, as many patients have abnormalities of brain development, and most patients have intellectual and developmental disability. Treatment aimed at the underlying metabolic defect, in addition to pyridoxine supplementation, has improved clinical outcomes. Recently discovered biomarkers and genetic testing allow for the diagnosis of PDE-ALDH7A1 without the need of a pyridoxine trial and hold the promise for newborn screening. Despite these many advances, PDE-ALDH7A1 remains a clinical and biochemical conundrum. The increasing use of model systems and an international collaboration of clinician-scientists are among the reasons to be optimistic that these questions will be answered in the near future and that the clinical outcomes and quality of life will continue to improve for patients with PDE-ALDH7A1.

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Quality and stability of extemporaneous pyridoxal phosphate preparations used in the treatment of paediatric epilepsy

Cited by 15 publications

References 29 publications

Development of a reversed phase liquid chromatographic method for analysis of pyridoxal‐5′‐phosphate and its impurities

Development of a reversed phase liquid chromatographic method for analysis of pyridoxal‐5′‐phosphate and its impurities

Disorders affecting vitamin B₆ metabolism

Pyridoxine‐dependent epilepsy: Current perspectives and questions for future research

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Quality and stability of extemporaneous pyridoxal phosphate preparations used in the treatment of paediatric epilepsy

Cited by 15 publications

References 29 publications

Development of a reversed phase liquid chromatographic method for analysis of pyridoxal‐5′‐phosphate and its impurities

Development of a reversed phase liquid chromatographic method for analysis of pyridoxal‐5′‐phosphate and its impurities

Disorders affecting vitamin B6 metabolism

Pyridoxine‐dependent epilepsy: Current perspectives and questions for future research

Contact Info

Product

Resources

About

Disorders affecting vitamin B₆ metabolism