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.
Gravel
Edmond
E
Department of Clinical Pharmacy, Institut Gustave Roussy, 39, rue Camille Desmoulins, 94800 Villejuif, France.
Bourget
Philippe
P
Mercier
Lionel
L
Paci
Angelo
A
D000970:Antineoplastic Agents / Q000032:analysis*; D002138:Calibration; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000032:analysis / Q000138:chemical synthesis* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002845:Chromatography; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002855:Chromatography, Thin Layer; D003720:Densitometry; D004345:Drug Industry / Q000379:methods*; D004355:Drug Stability; D000077146:Irinotecan; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000032:analysis; D011786:Quality Control; D015203:Reproducibility of Results; D013050:Spectrometry, Fluorescence / Q000379:methods*; D013678:Technology, Pharmaceutical; D019772:Topotecan / Q000032:analysis* / Q000737:chemistry
D000970:Antineoplastic Agents; D004364:Pharmaceutical Preparations; D000077146:Irinotecan; D019772:Topotecan; D002166:Camptothecin