Long-term Outcomes of Chemoradiation for Muscle-invasive Bladder Cancer in Noncystectomy Candidates. Final Results of NRG Oncology RTOG 0524-A Phase 1/2 Trial of Paclitaxel + Trastuzumab with Daily Radiation or Paclitaxel Alone with Daily Irradiation.

BACKGROUND: Chemo-radiation is a well-established alternative to radical cystectomy in patients with muscle-invasive bladder cancer. Many patients due to age or medical comorbidity are unfit for either radical cystectomy, or standard cisplatin- or 5-fluorouracil-based chemoradiation, and do not receive appropriate treatment with curative intent. We treated patients with a less aggressive protocol employing seven weekly doses of paclitaxel and daily irradiation. In those whose tumors showed overexpression of her2/neu, seven weekly doses of trastuzumab were also administered. OBJECTIVE: To report the long-term survival outcomes and toxicity results of the of NRG Oncology RTOG 0524 study. DESIGN, SETTING, AND PARTICIPANTS: Seventy patients were enrolled and 65 (median age: 76 yr) were deemed eligible. Patients were assigned to daily radiation and weekly paclitaxel + trastuzumab (group 1, 20 patients) or to daily radiation plus weekly paclitaxel (group 2, 45 patients) based on tumor her2/neu overexpression. Radiation was delivered in 1.8 Gy fractions to a total dose of 64.8 Gy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was unresolved treatment-related toxicity. The secondary endpoints were complete response rate, protocol completion rate, and disease-free and overall survival. RESULTS AND LIMITATIONS: Protocol therapy was completed by 60% (group 1) and 76% (group 2); complete response rates at 12 wk were 62% in each group. Acute treatment-related adverse events (AEs) of grade ≥3 were observed in 80% in group 1 and 58% in group 2. There was one treatment-related grade 5 AE in group 1. Unresolved acute treatment-related toxicity was 35% in group 1 and 31% in group 2. The median follow-up was 2.3 yr in all patients and 7.2 yr in surviving patients. Overall survival at 5 yr was 25.0% in group 1 and 37.8% in group 2 (33.8% overall). At 5 yr, disease-free survival was 15.0% in group 1 and 31.1% in group 2. CONCLUSIONS: In a cohort of patients with muscle-invasive bladder cancer who are not candidates for cystectomy or cisplatin chemotherapy, chemoradiation therapy offers a treatment with a significant response rate and 34% 5-yr overall survival. While there were many AEs in this medically fragile group, there were few grade 4 events and one grade 5 event attributable to therapy. PATIENT SUMMARY: Patients with invasive bladder cancer who cannot tolerate surgery were treated with radiation and systemic therapy without surgically removing their bladders. Most patients tolerated the treatment, were able to keep their bladders, and showed a significant treatment response rate.

A randomized, double-blind, placebo-controlled trial of testosterone for treatment of postmenopausal women with aromatase inhibitor-induced arthralgias: Alliance study A221102.

PURPOSE: To evaluate the efficacy of testosterone supplementation for improving aromatase inhibitor musculoskeletal symptoms (AIMSS). METHODS: Postmenopausal women experiencing moderate-to-severe arthralgias while taking adjuvant aromatase inhibitors for breast cancer were enrolled in this trial. Initially, patients were randomly allocated to receive either a subcutaneous testosterone pellet versus a placebo pellet. Due to slow accrual, the protocol was modified such that additional participants were randomized to receive either a topical testosterone gel or a placebo gel. Changes in patient-reported joint pain were compared between patients receiving testosterone and those receiving placebo using a two-sample t test. Changes in hot flashes and other vasomotor symptoms were also analyzed. Further analyses were conducted to evaluate whether 27 single nucleotide polymorphisms (SNPs) in 14 genes previously associated with AIMSS were associated with testosterone supplementation benefit. RESULTS: While 64% of patients reported an improvement in joint pain at 3 months, there were no significant differences in average pain or joint stiffness at 3 or 6 months between testosterone and placebo arms. Patients receiving testosterone did report improvements in strength, lack of energy, urinary frequency, and stress incontinence (p < 0.05). The subset of patients receiving subcutaneous testosterone also experienced improvements in hot flashes and mood swings. An inherited variant (rs7984870 CC genotype) in TNFSF11 was more likely to be associated with improvements in hot flashes in patients receiving testosterone. CONCLUSION: The doses of testosterone supplementation used in this study did not significantly improve AIMSS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01573442.

Results of NCCTG N0275 (Alliance) - a phase II trial evaluating resection followed by adjuvant radiation therapy for patients with desmoplastic melanoma.

To examine, in a prospective fashion, the utilization and efficacy of adjuvant radiation therapy (RT) in patients with resected desmoplastic melanoma (DM). Adult patients with resected, margin-negative, and nonmetastatic DM were eligible for this single-arm prospective phase II study. Patients were to receive postoperative RT, 30 Gy in five fractions, to the operative bed with 2- to 3-cm margins (depending on the tumor location). Nodal basin RT was not allowed. The primary study endpoint was the 2-year local recurrence rate (LRR). Secondary endpoints included the incidence of regional and distant metastatic disease, progression-free survival, overall survival (OS), and treatment-related toxicity. Twenty patients with a single de novo DM lesion meeting trial eligibility criteria were enrolled and treated. The 2-year LRR was 10%, with two patients demonstrating a LR within 2 years of completion of protocol therapy. No regional or distant failures occurred. OS at 2 and 5 years was 95 and 77%, respectively. There were no grade 3 or higher acute or late adverse events that were related to the protocol therapy. Adjuvant RT after wide local excision (WLE) for DM is efficacious and well tolerated. It should be considered for DM patients after margin-negative WLE. Additional study is needed to further refine low-risk patient populations that can potentially have adjuvant RT omitted as part of the treatment plan.

Survivorship care plans: is there buy-in from community oncology providers?

BACKGROUND: The Institute of Medicine recommended that survivors of cancer and their primary care providers receive survivorship care plans (SCPs) to summarize cancer treatment and plan ongoing care. However, the use of SCPs remains limited. METHODS: Oncology providers at 14 National Cancer Institute Community Cancer Centers Program hospitals completed a survey regarding their perceptions of SCPs, including barriers to implementation, strategies for implementation, the role of oncology providers, and the importance of topics in SCPs (diagnosis, treatment, recommended ongoing care, and the aspects of ongoing care that the oncology practice will provide). RESULTS: Among 245 providers (response rate of 70%), 52% reported ever providing any component of an SCP to patients. The most widely reported barriers were lack of personnel and time to create SCPs (69% and 64% of respondents, respectively). The most widely endorsed strategy among those using SCPs was the use of a template with prespecified fields; 94% of those who used templates found them helpful. For each topic of an SCP, although 87% to 89% of oncology providers believed it was very important for primary care providers to receive the information, only 58% to 65% of respondents believed it was very important for patients to receive the information. Furthermore, 33% to 38% of respondents reported mixed feelings regarding whether it was the responsibility of oncology providers to provide SCPs. CONCLUSIONS: Practices need additional resources to overcome barriers to implementing SCPs. We found resistance toward SCPs, particularly the perceived value for the survivor and the idea that oncology providers are responsible for SCP dissemination.

Assessment of patient-reported measures of bowel function before and after pelvic radiotherapy: an ancillary study of the North Central Cancer Treatment Group study N00CA.

PURPOSE: The Bowel Function Questionnaire (BFQ) has been used in clinical trials to assess symptoms during and after pelvic radiotherapy (RT). This study evaluated the importance of symptoms in the BFQ from a patient perspective. METHODS: Patients reported presence or absence of symptoms and rated importance of symptoms at baseline, 4 weeks after completion of pelvic RT, and 12 and 24 months after RT. The BFQ measured overall quality of life (QOL) and symptoms of nocturnal bowel movements, incontinence, clustering, need for protective clothing, inability to differentiate stool from gas, liquid bowel movements, urgency, cramping, and bleeding. Bowel movement frequency also was recorded. A content validity questionnaire (CVQ) was used to rate symptoms as "not very important," "moderately unimportant," "neutral," "moderately important," or "very important." RESULTS: Most of the 125 participating patients rated all symptoms as moderately or very important. Generally, patients gave similar ratings for symptom importance at all study points, and ratings were independent of whether the patient experienced the symptom. Measures of greatest importance (moderately or very important) at baseline were ability to control bowel movements (94 %), not having to wear protective clothing (90 %), and not having rectal bleeding (94 %). With the exception of need for protective clothing, the presence of a symptom at 4 weeks was associated with significantly worse QOL (P < .01 for all). CONCLUSIONS: The BFQ has excellent content validity. Patients rated most symptoms as moderately or very important, indicating the BFQ is an appropriate tool for symptom assessment during and after pelvic RT.

Role of different salts on cloud-point extraction of isoprocarb and promecarb insecticides followed by high-performance liquid chromatography.

The influence of salt additive on cloud point extraction (CPE) of isoprocarb and promecarb insecticides is described. Types of salt (Na(2)CO(3), CaCl(2), MgSO(4), Na(2)SO(4), NaHCO(3) and NaCl) and concentrations were studied. The extracted target compounds were analyzed using reversed phase high-performance liquid chromatography. Among the salts studied, Na(2)CO(3) was found to be the most effective salt for salting out of both insecticides, resulting in high extraction efficiency (>95%) and high enrichment factor of up to 18 compared to extraction without preconcentration. The optimum CPE conditions were 1.5% (w/v) Triton X-114, 3.0% (w/v) Na(2)CO(3), and 20-min equilibration at 45°C. Under the selected conditions, the linear range of 0.05 to 3.0 mg/L was found for both analytes. The limits of detection for isoprocarb and promecarb were 10 and 20 µg/L, respectively. High intra-day (n = 9) and inter-day (n = 3 × 4 days) precisions with relative standard deviations <1% and <8% were obtained for retention time and peak area, respectively. The proposed method was successfully applied for the residue analysis of target compounds in beverages (i.e., fruit juice, vegetable juice and wine samples), which provided high recoveries (>80%, on average) for spiked samples at three levels (0.05, 0.10 and 0.50 mg/L).

Sequential injection spectrophotometric determination of tetracycline antibiotics in pharmaceutical preparations and their residues in honey and milk samples using yttrium (III) and cationic surfactant.

A sequential injection analysis (SIA) spectrophotometric method for determining tetracycline (TC), chlortetracycline (CTC) and oxytetracycline (OTC) in different sample matrices were described. The method was based on the reaction between tetracyclines and yttrium (III) in weak basic micellar medium, yielding the light yellow complexes, which were monitored at 390, 392 and 395 nm, respectively. A cationic surfactant, cetyltrimethylammonium bromide (CTAB) was used to obtain the micellar system. The linear ranges of calibration graphs were between 1.0 × 10(-5) and 4 × 10(-4) mol L(-1), respectively. The molar absorptivities were 5.24 × 10(5), 4.98 × 10(4) and 4.78 × 10(4) L mol(-1)cm(-1). The detection limits (3σ) were between 4.9 × 10(-6) and 7.8 × 10(-6) mol L(-1) whereas the limit of quantitations (10σ) were between 1.63 × 10(-5) and 2.60 × 10(-5) mol L(-1) the interday and intraday precisions within a weak revealed as the relative standard deviations (R.S.D., n=11) were less than 4%. The method was rapid with a sampling rate of over 60 samples h(-1) for the three drugs. The proposed method has been satisfactorily applied for the determination of tetracycline and its derivatives in pharmaceutical preparations together with their residues in milk and honey samples collected in Chiang Mai Province. The accuracy was found to be high as the Student's t-values were found to be less than the theoretical ones. The results were compared favorably with those obtained by the conventional spectrophotometric method.

Comparison of provider-assessed and patient-reported outcome measures of acute skin toxicity during a Phase III trial of mometasone cream versus placebo during breast radiotherapy: the North Central Cancer Treatment Group (N06C4).

PURPOSE: Considerable interobserver variability exists among providers and between providers and patients when measuring subjective symptoms. In the recently published Phase III N06C4 trial of mometasone cream vs. placebo to prevent radiation dermatitis, the primary provider-assessed (PA) endpoint, using the Common Toxicity Criteria for Adverse Events (CTCAE), was negative. However, prospectively planned secondary analyses of patient-reported outcomes (PROs), using the Skindex-16 and Skin Toxicity Assessment Tool (STAT), were positive. This study assesses the relationship between PA outcomes and PROs. METHODS AND MATERIALS: Pearson correlation coefficients were calculated to compare the three tools. Statistical correlations were defined as follows: <0.5, mild; 0.5-0.7, moderate; and >0.7, strong. RESULTS: CTCAE dermatitis moderately correlated with STAT erythema, and CTCAE pruritus strongly correlated with STAT itching. CTCAE pruritus had a moderate correlation with Skindex-16 itching. Comparing the 2 PRO tools, Skindex-16 itching correlated moderately with STAT itching. Skindex-16 burning, hurting, irritation, and persistence all showed the strongest correlation with STAT burning; they showed moderate correlations with STAT itching and tenderness. CONCLUSIONS: The PRO Skindex-16 correlated well with the PRO portions of STAT, but neither tool correlated well with CTCAE. PROs delineated a wider spectrum of toxicity than PA measures and provided more information on rash, redness, pruritus, and annoyance measures compared with CTCAE findings of rash and pruritus. PROs may provide a more complete measure of patient experience than single-symptom, PA endpoints in clinical trials assessing radiation skin toxicity.

Mometasone furoate effect on acute skin toxicity in breast cancer patients receiving radiotherapy: a phase III double-blind, randomized trial from the North Central Cancer Treatment Group N06C4.

PURPOSE: A two-arm, double-blind, randomized trial was performed to evaluate the effect of 0.1% mometasone furoate (MMF) on acute skin-related toxicity in patients undergoing breast or chest wall radiotherapy. METHODS AND MATERIALS: Patients with ductal carcinoma in situ or invasive breast carcinoma who were undergoing external beam radiotherapy to the breast or chest wall were randomly assigned to apply 0.1% MMF or placebo cream daily. The primary study endpoint was the provider-assessed maximal grade of Common Terminology Criteria for Adverse Events, version 3.0, radiation dermatitis. The secondary endpoints included provider-assessed Common Terminology Criteria for Adverse Events Grade 3 or greater radiation dermatitis and adverse event monitoring. The patient-reported outcome measures included the Skindex-16, the Skin Toxicity Assessment Tool, a Symptom Experience Diary, and a quality-of-life self-assessment. An assessment was performed at baseline, weekly during radiotherapy, and for 2 weeks after radiotherapy. RESULTS: A total of 176 patients were enrolled between September 21, 2007, and December 7, 2007. The provider-assessed primary endpoint showed no difference in the mean maximum grade of radiation dermatitis by treatment arm (1.2 for MMF vs. 1.3 for placebo; p = .18). Common Terminology Criteria for Adverse Events toxicity was greater in the placebo group (p = .04), primarily from pruritus. For the patient-reported outcome measures, the maximum Skindex-16 score for the MMF group showed less itching (p = .008), less irritation (p = .01), less symptom persistence or recurrence (p = .02), and less annoyance with skin problems (p = .04). The group's maximal Skin Toxicity Assessment Tool score showed less burning sensation (p = .02) and less itching (p = .002). CONCLUSION: Patients receiving daily MMF during radiotherapy might experience reduced acute skin toxicity compared with patients receiving placebo.

Brain metastases from melanoma: is there a role for concurrent temozolomide in addition to whole brain radiation therapy?

OBJECTIVES: This study was performed to evaluate the addition of temozolomide (TMZ) to whole brain radiotherapy (WBRT) for brain metastases from melanoma. METHODS: Seven patients with brain metastases from melanoma were treated on a North Central Cancer Treatment Group (NCCTG) trial (N0274) of TMZ plus WBRT. TMZ was given orally in doses of 200 mg/m² for 5 days every 4 weeks for up to 8 cycles. WBRT was started on the first day of TMZ and included the delivery of 3750 cGy in 15 fractions. In addition, separately analyzed was a cohort of 53 patients treated at the Mayo Clinic who received WBRT alone (39 patients) or WBRT plus TMZ (14 patients). RESULTS: The median survival of the 7 patients treated on N0274 was 3.6 months with 2 of 7 (29%) failing in brain and 5 of 7 (71%) failing elsewhere. For the other cohort of 53 patients, the median survival was 3.8 months with WBRT alone compared 4.3 months for WBRT plus TMZ (P = 0.5). CONCLUSIONS: Patients did not appear to benefit from the addition of TMZ to WBRT for the treatment of their brain metastases. Further improvements in outcome will require research to discover more effective systemic therapy and RT techniques.

Prognostic factors differ by tumor stage for small cell lung cancer: a pooled analysis of North Central Cancer Treatment Group trials.

BACKGROUND: An analysis of 14 small cell lung cancer (SCLC) trials was performed to improve the current understanding of potential prognostic factors for overall survival (OS) and progression-free survival (PFS) in groups of patients with limited-stage disease SCLC (LD-SCLC) and extensive-stage disease SCLC (ED-SCLC) separately. METHODS: Data on 688 patients with LD-SCLC and 910 patients with ED-SCLC were included. Clinical and laboratory factors were tested for their prognostic significance using Cox regression models that were stratified by protocol. Recursive partitioning and amalgamation (RPA) analyses were used to identify prognostic subgroups. RESULTS: Poorer performance status (PS) led to worse OS and PFS in the ED-SCLC group but not in the LD-SCLC group. The prognostic impact of PS was strong for men but weak for women in the ED-SCLC group (interaction P value <.012 for OS and PFS). Other negative prognostic factors included increased age and men for the LD-SCLC group and increased age, men, increased number of metastatic sites at baseline, and increased creatinine levels for the ED-SCLC group. In patients with the ED-SCLC, RPA analyses identified 5 subgroups with different prognosis based on baseline PS, creatinine levels, sex, and the number of metastatic sites. CONCLUSIONS: The current pooled analysis identified baseline creatinine levels and the number of metastatic sites as important prognostic factors in patients with ED-SCLC in addition to the well established factors of sex, age, and PS. There was a significant interaction between sex and PS within the ED-SCLC group, suggesting that PS is highly prognostic in men but has no significant impact in women. Within the LD-SCLC group, only age and sex were identified as important prognostic factors. RPA analyses confirmed many of these findings.

Cloud-point extraction and reversed-phase high-performance liquid chromatography for the determination of carbamate insecticide residues in fruits.

A cloud-point extraction (CPE) method using Triton X-114 non-ionic surfactant was developed for the extraction and preconcentration of carbamate insecticide residues (i.e., methomyl, propoxur, carbofuran, carbaryl, isoprocarb, and promecarb) in fruit samples. The optimum conditions of CPE were 1.5% (w/v) Triton X-114, 7.0% (w/v) NaCl and 20 min equilibrated at 45 degrees C. The surfactant-rich phase was then analyzed by reversed-phase high-performance liquid chromatography with ultraviolet detection at 270 nm, under gradient separation using methanol and 0.1% (v/v) acetic acid. Under the study conditions, six carbamate insecticides were successfully separated within 27 min. Good reproducibility was obtained with the relative standard deviation of <3% for retention time and <9% for peak area. Limits of detection in the studied fruit samples were in the range of 0.1-1.0 mg kg(-1). No carbamate insecticides were detected in the studied fruit samples. The high recoveries of the spiked fruit samples were obtained in the range 80.0-107%. The CPE method has been shown to be a potential useful methodology for the preconcentration of the target analytes, with a preconcentration factor of 14. Moreover, the method is simple, has high sensitivity, consumes much less solvent than traditional methods, and is environmental friendly.

Phase III, double-blind study of depot octreotide versus placebo in the prevention of acute diarrhea in patients receiving pelvic radiation therapy: results of North Central Cancer Treatment Group N00CA.

PURPOSE: To assess the effectiveness of depot octreotide for the prevention of diarrhea during pelvic radiation therapy. PATIENTS AND METHODS: Patients receiving pelvic radiation therapy (planned minimum dose, 45 Gy; 1.7 to 2.1 Gy daily) were eligible for the study. From May 10, 2002, through October 14, 2005, 125 patients were randomly allocated in a double-blind fashion to receive octreotide (100 microg, administered subcutaneously on day 1, followed by depot octreotide, 20 mg, administered intramuscularly on days 2 and 29; n = 62) or to receive a placebo (n = 63). RESULTS: Grade 0, 1, 2, and 3 diarrhea were observed in 18%, 31%, 31%, and 21% of patients in the octreotide arm, respectively, and in 25%, 32%, 22%, and 21% of patients in the placebo arm, respectively (P = .64). Grade 0, 1, 2, and 3 abdominal cramps were observed in 32%, 45%, 21%, and 2% of patients receiving octreotide, respectively, and in 51%, 24%, 21%, and 5% of patients receiving the placebo, respectively (P = .053). Some patient-reported symptoms were worse in the octreotide group, including nocturnal bowel movements (70% v 45%; P = .004), clustering of bowel movements (90% v 69%; P = .004), and bleeding with bowel movements (57% v 35%; P = .01). CONCLUSION: As administered in this study, octreotide did not decrease diarrhea during pelvic radiation therapy. Some gastrointestinal symptoms were worse in patients treated with octreotide. Octreotide is not indicated for prevention of diarrhea during pelvic radiation therapy.

The value of combined-modality therapy in elderly patients with stage III nonsmall cell lung cancer.

BACKGROUND: The objective of this study was to assess the value of combined-modality therapy in elderly patients by comparing the differences in outcome between patients who received radiotherapy (RT) alone and patients who received RT plus chemotherapy for stage III nonsmall cell lung cancer (NSCLC). METHODS: The North Central Cancer Treatment Group performed 2 recent Phase III trials for stage III NSCLC. The first trial, NCCTG 90-24-51, included 3 arms: once-daily RT (QDRT) alone, twice-daily RT (BIDRT) alone, and concurrent chemotherapy plus BIDRT. The second trial, NCCTG 94-24-52, included 2 arms and compared concurrent chemotherapy with either QDRT or BIDRT. The chemotherapy arms of both trials included etoposide and cisplatin administered concurrently with RT. Only the patients aged >/=65 years (elderly) who participated in those trials were included in this analysis. RESULTS: Of the 166 elderly patients who were included in this analysis, 37 patients received RT alone, and 129 patients received concurrent chemotherapy plus RT. The median and 5-year survival rates were 10.5 months and 5.4% for the RT alone group compared with 13.7 months and 14.7% for the RT plus chemotherapy group (log-rank P = .05). Patients who received RT plus chemotherapy experienced significantly greater severe toxicity (grade >/=3) compared with patients who received RT alone (89.9% vs 32.4%; P < 0.01). CONCLUSIONS: Elderly patients who participated in these trials appeared to gain a survival advantage from RT and chemotherapy compared with RT alone. As is the case with younger patients, this benefit came at the cost of additional toxicity.

Results of combined-modality therapy for limited-stage small cell lung carcinoma in the elderly.

BACKGROUND: A Phase III trial was conducted by the North Central Cancer Treatment Group to determine whether chemotherapy (etoposide and cisplatin) plus either twice-daily radiotherapy (BIDRT) or once-daily radiotherapy (QDRT) resulted in a better outcome for patients with limited-stage small cell lung carcinoma (LD-SCLC). No difference in survival was identified between the two arms. The current analysis examined the relation between age and outcome for patients treated during this trial. METHODS: The current study included 263 patients with LD-SCLC and an Eastern Cooperative Oncology Group performance status of < or = 2 who were randomized to receive QDRT or split-course BIDRT. The outcomes of the 209 (79%) younger patients (age < 70 years old) were compared with the 54 (21%) elderly patients (age > or = 70 years old). RESULTS: Elderly patients presented with significantly greater weight loss and poorer performance status. The 2-year and 5-year survival rates were 48% and 22% for younger patients compared with 33% and 17% for older patients (P = 0.14). One specific toxicity (i.e., Grade > or = 4 pneumonitis [according to National Cancer Institute Common Toxicity Criteria]) occurred in 0% of those patients age < 70 years compared with 6% of older patients (P = 0.008). Grade 5 toxicity occurred in 1 of 209 (0.5%) patients age < 70 years compared with 3 of 54 (5.6%) older patients (P = 0.03). CONCLUSIONS: Despite having more weight loss, poorer performance status, increased pulmonary toxicity, and more deaths due to treatment, survival was not found to be significantly worse in older individuals. Fit elderly patients with LD-SCLC can receive combined-modality therapy with the expectation of relatively favorable long-term survival. Future research should focus on ways to decrease toxicity especially in the elderly.

Theoretical study of hydrogen-bonded complexes of chlorophenols with water or ammonia: Correlations and predictions of pKa values.

A simple practical method for predicting the acidity constants (as pKa values) of chlorophenols is proposed based on density functional theory calculations of a series of hydrogen-bonded complexes of phenol and 19 different congeners of chlorophenol, with a single probe molecule, either water or ammonia. Relevant structural parameters and molecular properties of these complexes, primarily involving the acidic hydroxyl group, are examined and plotted against the known pKa values of 14 chlorophenols and phenol. Strong linear correlations are found for these compounds. Such correlations are used to determine the pKa values of five chlorophenols whose experimental acidities have large uncertainties. Similar predicted pKa values are obtained by using different structural parameters and molecular properties for the complexes with either probe molecule. The study may be extended to determine the acidity of other compounds with a single acidic functional group.

Enhanced sensitivity and selectivity in the detection of polycyclic aromatic hydrocarbons using sequential simplex optimization, the addition of an organic modifier and wavelength programming.

Optimized separation of a mixture of 16 priority pollutant polycyclic aromatic hydrocarbons (PAHs) by high performance liquid chromatography (HPLC) using the sequential simplex optimization method was accomplished by varying the starting and ending compositions of acetonitrile and water, linear gradient time, mobile phase flow rate, column temperature and holding time of the final mobile phase composition. Focusing on the two sets of difficult-to-separate pairs (acenaphthene-fluorene and benzo[g,h,i]perylene-indeno[1,2,3-c,d]pyrene), analysis time was reduced by about ten percent through the use of an organic modifier (isopropanol or methanol), under both optimum and near-optimum conditions, while maintaining good separation of the remaining PAHs. High sensitivity for all of the 16 PAHs was achieved by wavelength programming during elution using five wavelengths (224, 235, 254 270 and 296 nm), depending upon the molar absorptivities of the individual compounds. Detection limits (DLs) ranging from 0.002 (benzo[a]pyrene) to 0.140 mug ml(-1) (acenaphthene) were achieved for this set of 16 standard compounds.

Use of the simplex method to optimize the mobile phase for the micellar chromatographic separation of inorganic anions.

The sequential simplex strategy has been used to optimize the mobile phase used for separation of inorganic anions by micellar chromatography on a C(18)- micro Bondapak column, with absorption detection at 230 nm. The amount of acetonitrile and the concentration of phosphate buffer (pH 6.0) were chosen for optimization. The optimum mobile phase was found to be 38% acetonitrile in 18.2 mmol L(-1) phosphate buffer (pH 6.0) containing 10 mmol L(-1) cetyltrimethylammonium bromide (CTAB); this optimum was achieved within seven experiments. The separation of the five anions (nitrite, nitrate, iodide, thiocyanate, and thiosulfate) was accomplished in 18 min.

Simplex optimization of ion-pair reversed-phase high performance liquid chromatographic analysis of some heavy metals.

The sequential simplex algorithm was used to optimize the ion-pair reversed phase high performance liquid chromatographic (IP-RPHPLC) analysis of 4-(2-pyridylazo)resorcinol (PAR) chelates of Co(II), Ni(II) and Cr(III). A chromatographic response function (CRF) which included the number of peaks, the resolution between adjacent peaks, a specified analysis time, and the individual retention times relative to a minimum retention time, was calculated to evaluate the quality of the individual chromatograms. The optimum conditions for the three experimental parameters were 28.6% acetonitrile in the mobile phase, 3.0 mmol l(-1) concentration of acetate buffer at pH 6.0, and 5.2 mmol l(-1) tetrabutylammonium bromide (TBABr). Optimum conditions were achieved in only 19 experiments. The order of elution was Co(II)PAR, Cr(III)PAR and Ni(II)PAR, respectively, with an analysis time of 15 min.