Microbiological and physicochemical stability of fentanyl and sufentanil solutions for patient-controlled delivery systems.

The aim of this study was to assess the microbiological and physicochemical stability of opioid solutions containing fentanyl or sufentanil and thereby determine the feasibility of extending the expiration dates after mixing. Five systems containing fentanyl or sufentanil solutions at 50 microg/mL in portable patient-controlled analgesia (PCA) systems were filled and stored at room temperature for 14 days. They were sampled immediately after preparation, at day 3, and each day of the following weeks. Microbiological stability was assessed by performing sterility tests. The physicochemical study was performed by determining aspect, pH, and osmolality evolution. All samples were tested for appearance, change in color, and loss of concentration using an analytical method. There was no significant change in pH and osmolality values of any solutions. No precipitation or change in color was observed in any of the sample solutions. There was no significant loss of fentanyl or sufentanil over 14 days (4.3% and 4.1%, respectively). This study indicates that both drug solutions in the PCA systems are stable for a minimum of 14 days at room temperature.

Application of an acceptance sampling plan for post-production quality control of chemotherapeutic batches in an hospital pharmacy.

BACKGROUND: About 26,000 chemotherapeutic batches were produced in 2003 in the Institute Gustave Roussy and 83% were qualitatively and quantitatively assessed in post-production controls via an analytical platform. The rate of non-conformity (outside the specification limits of the target concentration +/-10%) decreased from 8.9% to 2.2% between years 2001 and 2003. A cost- and time-saving acceptance sampling plan was applied to assay fewer batches whilst maintaining an accurate estimate of the quality level. METHODS: The opportunity to apply a single sampling plan by attributes with an acceptance quality level of 2.2% was evaluated. A prognostic study using a logistic regression model was performed for some drugs to identify risk factors associated with the non-conformity rate of preparations. RESULTS: Out of 26 drugs, 17 have not been sampled, since they were prepared less than 400 times per year. For six drugs, a reduction of about 50% in the number of assays was estimated. Three drugs were "at risk" of being non-conform: for these drugs, all batches were analysed. CONCLUSIONS: The sampling plan allowed a reduction of almost 8000 analyses with respect to the number of batches analysed for 6 drugs. For the 3 drugs with the higher risk to be non-conform, associated risk factors were identified to set up corrective actions.

Photodynamic efficiency of diethylene glycol-linked glycoconjugated porphyrins in human retinoblastoma cells.

Photodynamic therapy (PDT) is emerging as a new strategy for the conservative treatment of hereditary retinoblastoma. The glycoconjugated porphyrins TPP(p-Deg-O-alpha-GalOH)(3), TPP(p-Deg-O-beta-GalOH)(3), TPP(p-Deg-O-alpha-ManOH)(3), and their S-analogues were synthesized to obtain efficient photosensitizers with some retinoblastoma cell affinity. In these systems, a sugar motif and porphyrin core were linked by a diethylene glycol spacer (Deg). Cellular uptake, localization, and photoactivity have been examined in human retinoblastoma cells (Y79). After preincubation with corresponding glycosylated albumin, the uptake of TPP(p-Deg-O-beta-GalOH)(3) and TPP(p-Deg-O-alpha-ManOH)(3) was 40-45% inhibited, indicating a possible cell-sugar-receptor saturation. High photoactivity was observed for the two alpha-galacto/manno porphyrins 8 and 10 (LD(50) = 0.05 and 0.35 muM, respectively) at 514 nm and low fluence (1 J/cm(2)). Analysis by MALDI-TOF mass spectrometry only indicated a small metabolic cleavage of the O-glycoconjugates and a good stability of the S-glycoside porphyrins. On the basis of these in vitro data, TPP(p-Deg-O-alpha-GalOH)(3) and TPP(p-Deg-O-alpha-ManOH)(3) were selected for in vivo studies.

Quality control and stability study using HPTLC: applications to cyclophosphamide in various pharmaceutical products.

Cyclophosphamide is an alkylating agent widely used from cancer chemotherapy to immunotherapy purposes. In paediatrics oncology, oral cyclophosphamide prescribed at low dosages for a long time treatment is currently investigated. This treatment is a putative well tolerated regimen for children treated for a wide variety of recurrent solid tumours. For these purposes, new oral formulations more convenient for children than cyclophosphamide 50mg tablets are needed. Thus, we present a rapid method for the assay of cyclophosphamide in various pharmaceutical preparations using high-performance thin-layer chromatography (HPTLC) and derivatization with phosphomolybdic acid. This method is accurate and precise and allows quantitation of cyclophosphamide in aqueous solutions from 400 to 1200 microg/mL. It is suitable for quantitation and stability studies of cyclophosphamide in pharmaceutical products, i.e. capsules and infusion bags prepared in a hospital pharmacy. According to pharmaceutical guidelines, we demonstrated that low dose cyclophosphamide capsules, extemporaneously prepared for children, are stable at least for 70 days.

5-aminolevulinic acid ester-induced protoporphyrin IX in a murine melanoma cell line.

The use of 5-aminolevulinic acid (5-ALA) ester derivatives as precursors of endogenous protoporphyrin IX (PpIX) has been proposed as a good strategy for improved drug diffusion across biological membranes. In the present work, the 5-ALA ester derivatives hexyl-ALA (h-ALA), octyl-ALA (o-ALA), and decyl-ALA (d-ALA) were synthesized, and their efficacy to induce endogenous PpIX was explored in a murine melanoma cell line (B-16) as compared with that of 5-ALA. The maximum level of PpIX induced in cells treated with 5-ALA, h-ALA, o-ALA, and d-ALA was reached at optimal concentrations of 0.3, 0.075, 0.1, and 0.075 mM, respectively. The derivatives h-ALA and o-ALA appear as the most efficient PpIX precursors in this cell line, since a higher or similar PpIX production could be achieved with a fourfold and threefold lower dose of these precursors compared with 5-ALA. The phototoxicity effect of h-ALA and o-ALA ester derivatives showed the same phototoxicity behavior detected for 5-ALA but at much lower drug doses. Our study suggests that h-ALA and o-ALA esters improve intracellular PpIX formation in B-16 cells at reduced concentrations. This should enable clinical applications at lower precursor doses with reduced effective costs.