Biomedical subjects

Philippe Bourget

Publications and source records attributed to Philippe Bourget.

7 recordsLinked to original sources

PubMed2005

Fluorescence detection combined with either HPLC or HPTLC for pharmaceutical quality control in a hospital chemotherapy production unit: application to camptothecin derivatives.

In order to achieve the analytical assessment of the manufactured batches of chemotherapy preparations, post-production quality control has been developed. The common use of camptothecin derivatives (i.e. irinotecan (CPT-11) and topotecan (TPT)) as part of protocols in Institut Gustave Roussy (IGR) has led to develop an efficient analytical method that could assess an increasing number of samples with high throughput, good specificity and practicality. Due to the difference of concentration between batches containing irinotecan or topotecan, HPLC and HPTLC both combined with fluorescence detection were investigated. Those two techniques made identity, purity and quantitation assays possible. The chromatographic conditions that were chosen allowed identification of each drug through their rate of flow (Rf), 0.10 and 0.35, or their retention time (tR), 2 and 7 min for topotecan and irinotecan, respectively. A calibration curve was plotted for each molecule and validated by three quality controls (high, medium and low). Coefficients of variation of repeatability (CVr) and intermediate precision (CVi) were determined for both methods. Considering their values and the concentration ranges (from 100 to 500 mg/L for HPTLC and from 0.1 to 1 mg/L for HPLC), it was decided to perform analysis using HPTLC for irinotecan preparations and HPLC for topotecan preparations. These inferences seemed appropriate regarding the number of preparations to be assayed.

Antineoplastic Agents↗

PubMed2005

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.

Calibration↗

PubMed2005

Liquid chromatography-mass spectrometry assay for quantitation of ifosfamide and its N-deschloroethylated metabolites in rat microsomal medium.

A specific and sensitive quantitative assay has been developed using high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS) for the simultaneous quantitation of the antitumor drug ifosfamide (IFM) and its two metabolites, N2-deschloroethylifosfamide (N2-DCE-IFM) and N3-deschloroethylifosfamide (N3-DCE-IFM) in microsomal medium. The analytes and the internal standard (cyclophosphamide) were isolated by ethylacetate extraction from rat liver microsomes. They were analysed on a Nucleosil C18 HD column (125 mm x 4 mm, 5 microm) using a step gradient with the mobile phase (2 mM ammonium formate and methanol). The HPLC-ESI-MS method used selected ion monitoring of ions m/z 199.1 Th and m/z 261.1 Th and was validated in the concentrations ranges of 100-5000 ng/mL for IFM and 50-2500 ng/mL for its N-deschloroethylated metabolites (DCE-IFM) with good accuracy and precision (CV less than 15%). The low limits of quantitation (LLOQ) were found at 50 ng/mL for N-deschloroethylated metabolites and at 100 ng/mL for the parent drug (IFM). The method was applied for the determination of ifosfamide and its N-deschloroethylated metabolites in rat microsomal incubations.

Animals↗

PubMed2005

In vitro echogenicity characterization of poly[lactide-coglycolide] (plga) microparticles and preliminary in vivo ultrasound enhancement study for ultrasound contrast agent application.

OBJECTIVES: This work includes (1) the characterization of a reproducible poly[lactide-coglycolide] (PLGA) microparticle preparation with an optimial mean diameter and size distribution and (2) the preliminary in vivo ultrasonographic investigation of PLGA microparticles. METHODS: A first series of PLGA microparticle preparations (1 to 15 mum) was acoustically characterized on a hydrodynamic device to select the most appropriate for ultrasound contrast agent application. Preparations of 3-microm microparticles were selected, characterized at different doses, and then injected into 20 melanoma grafted mice for contrast-enhanced power Doppler ultrasonography evaluation. RESULTS: The 3-microm microparticles (3.26-microm mean diameter with 0.41-microm standard deviation) led to in vitro enhancement of 18.3 dB at 0.62 mg/mL. In vivo experiments showed 47% enhancement of intratumoral vascularization detection after PLGA injection, significantly correlated (P < 0.0001) with preinjection intravascularization and tumoral volume. No toxicity was histologically observed. CONCLUSION: The 3-microm PLGA microparticles provided significant enhancement in vitro and in vivo without any toxicity.

Animals↗

PubMed2004

Incidence of renal insufficiency in cancer patients and evaluation of information available on the use of anticancer drugs in renally impaired patients.

BACKGROUND: Chronic renal failure is a common pathology. The high frequency of this disease in the general US population has been assessed in the NHANES III study. However, the frequency of chronic renal insufficiency among cancer patients remains unclear. MATERIAL/METHODS: 316 cancer patients were in a one-month study, included regardless of their pathology, treatment (antineoplastic drugs used or programmed to be used, pretreated, or no treatment), or any other criteria. RESULTS: Among the patients, 287 (90.8%) had normal serum creatinine levels (<110 micromol/l), i.e. a frequency of 9.2% for renal insufficiency in our population. However, when renal function was estimated by calculating creatinine clearance using the Cockcroft and Gault formula, 33% of the patients had an estimated GFR of less than 80 ml/min. Among these, 28% had a creatinine clearance ranging form 80 to 50 ml/min and 5% had a creatinine clearance of less than 50 ml/min. Renal insufficiency is frequent in cancer patients since almost one third of the patients present renal insufficiency. Furthermore, among patients with normal serum creatinine levels, one patient out of five has asymptomatic renal insufficiency. CONCLUSIONS: Therefore, it is of major importance that renal function be assessed by calculation of creatinine clearance using the Cockcroft and Gault formula in every patient, even when serum creatinine is within the normal range.

Aged↗

PubMed2004

High-performance thin-layer chromatography with a derivatization procedure, a suitable method for the identification and the quantitation of busulfan in various pharmaceutical products.

Busulfan is an alkylating agent widely used in combination chemotherapy regimens followed by allogeneic or autologous hematopoietic stem cell transplantation (HSCT). We present a rapid method for assaying busulfan in pharmaceutical preparations using high-performance thin-layer chromatography (HPTLC) and derivatization with 4-nitrobenzylpyridine. The method is accurate and precise and allows quantitation of busulfan in aqueous solutions from 100 to 500 microg/ml. It is suitable for identification. quantitation and stability studies of busulfan in pharmaceutical products, i.e. capsules or infusion bags prepared in a hospital pharmacy.

Busulfan↗

PubMed2003

Contribution of high-performance thin-layer chromatography to a pharmaceutical quality assurance programme in a hospital chemotherapy manufacturing unit.

The Department of Clinical Pharmacy (DCP) in the Institut Gustave-Roussy (IGR) is equipped with a high-performance thin-layer chromatography (HPTLC) analytical platform. One of the numerous possible uses of HPTLC is post-production quality control of chemotherapy manufacturing. After 3 years of existence, routine validation of manufactured batches has attained considerable maturity: 24 cytotoxic agents can be controlled in terms of identity, purity and concentration. Approximately 50% of the sampled preparations are assessed. More than 97% were within specifications, 1.6% were not, probably due to incorrect homogenization before sampling; and 1% were not evaluable. Using HPTLC in a hospital manufacturing unit contributes to quality assurance programmes such as accreditation to which the IGR DCP is now committed but also ISO 9001:2000 certification concerning the chemotherapy manufacturing unit.

Chromatography, High Pressure Liquid↗