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Publications (4)1.53 Total impact

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    ABSTRACT: A chiral procedure based on electrokinetic chromatography was developed and validated for sumanirole (PNU‐95666E), a drug candidate that was under development for treatment of Parkinson's disease. The method underwent various iterations over a several years’ period, first utilizing a neutral cyclodextrin as the chiral recognition agent, then later using a highly sulfated‐beta‐cyclodextrin (HS‐β‐CD). Separation is on a 61 cm×50 µm ID fused silica capillary at an applied potential of −25 kV with a background electrolyte of 5% HS‐β‐CD in pH 2.50, 22.5 mM lithium phosphate buffer. For a sample prepared at 5 mg/mL, the limit of detection (LOD) for the undesired enantiomer (distomer) is about 0.02%. In a similar method developed for a congener of sumanirole, the LOD is approximately 0.01%, but at a sample concentration of 10 mg/mL. The separation, in both cases, takes less than 20 min. Over the range of 0.05–0.4%, the average recovery for the distomer of sumanirole was 102.1% and the linear regression correlation coefficient (r) 0.9999. For the congener over the range of 0.1–1.8%, a correlation coefficient of 0.9999 and an average recovery of 105.2% were obtained. The sumanirole method in its several iterations was used to collect four years of ICH stability data on the active pharmaceutical ingredient (API). No sample, either in the ICH study or any other lot manufactured over the years, yielded a value above 0.05% for the distomer. The method was additionally used to assess chiral inversion in API and in several formulations.
    Journal of Liquid Chromatography &amp Related Technologies 01/2006; 29(12):1703-1724. · 0.57 Impact Factor
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    ABSTRACT: A method based on micellar electrokinetic capillary chromatography (MEKC) was developed for determination of minoxidil in Rogaine and competing products. The original intent of the work was to offer an orthogonal means to HPLC for testing illicit imitations of Rogaine. However, because the patent has since expired, we offer the procedure as a confirmatory measure to HPLC for assay of generic minoxidil products. The MEKC procedure complements an earlier method based on free solution capillary electrophoresis (FSCE), designed to the same end. Validation was carried out on both a Dionex CES-1, which utilizes gravity injection, and a PE-ABI 270HT, which employs vacuum injection. The procedure was validated for both active pharmaceutical ingredient and for minoxidil solutions. The run buffer is pH 7.0, 20 mM sodium phosphate, 20 mM sodium dodecyl sulfate, with 10% isopropanol; the internal standard is dl-tryptophan. The method bears the attributes of simplicity, ease of use, and short analysis time (12 min). It is selective with respect to known process and degradation impurities. High efficiency was achieved on the CES-1, with a plate count exceeding 200,000 for minoxidil at an elution time of 9 min. Although slight differences in performance were noted across the two instruments, results on both were in conformance with modern day validation expectations. Comparison of MEKC with HPLC resulted in slightly higher values for the former, but all results met registration specifications and internal targets.
    Il Farmaco 11/2005; 60(10):847-53.
  • K. A. Mills, T. Ramstad
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    ABSTRACT: The odor in sterile solution lincomycin hydrochloride (S.S. Lincocin) subjected to terminal heat sterilization is due primarily to methyl mercaptan (CH3SH), secondarily to dimethyl disulfide (DMDS). Methyl mercaptan is generated by cleavage of the methyl mercaptyl group from the pyranoside ring in lincomycin; DMDS results from subsequent oxidation of CH3SH. A splitless headspace GC method was developed to detect and quantify the two compounds. Peak identification was made by injection of authentic standards in conjunction with chromatographic sniffing. CH3SH and DMDS were quantified by standard addition and were found to be present at about 1 and 0.05 ppm, respectively, in a lincomycin solution heated at 80°C for 30 minutes. These levels are well above the documented odor thresholds for these two compounds in water. In contrast, no CH3SH was detected over unheated lincomycin. The amounts of CH3SH and DMDS generated correspond to a 0.003% decrease in drug concentration.
    Analytical Letters 01/1996; 29(2):265-281. · 0.97 Impact Factor
  • S C Patterson, T Ramstad, K A Mills
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    ABSTRACT: A high performance capillary electrophoresis method was developed and validated for purity assessment of minoxidil bulk drug and for determination of minoxidil in Rogaine. The principal use of the method was in analyzing illicit minoxidil-containing hair-regrowth samples. Although validated for Rogaine, the procedure proved equally viable on illicit minoxidil-containing preparations. The developed method fulfilled the goal of providing an orthogonal technique to HPLC for confirmation of the presence of minoxidil in these imitations. The method was validated on two instruments, one utilizing EK injection, the other gravity injection. It is selective for minoxidil, which is separated from known process impurities and the single degradation impurity. Validation figures of merit for linearity/recovery (accuracy) and precision were in accordance with current expectations for method validation.
    Il Farmaco 60(6-7):547-54.