Preclinical and phase I clinical studies with the nonclassical antifolate thymidylate synthase inhibitor nolatrexed dihydrochloride given by prolonged administration in patients with solid tumors.

1998 ◽  
Vol 16 (3) ◽  
pp. 1131-1141 ◽  
Author(s):  
I Rafi ◽  
A V Boddy ◽  
J A Calvete ◽  
G A Taylor ◽  
D R Newell ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Thymidylate Synthase ◽  
High Performance ◽  
Plasma Concentrations ◽  
Maximum Tolerated Dose ◽  
Hematologic Toxicity ◽  
Antitumor Effects

PURPOSE A phase I, multicenter trial of the thymidylate synthase (TS) inhibitor THYMITAQ (nolatrexed dihydrochloride; Agouron Pharmaceuticals, Inc, San Diego, CA) given by 5-day continuous infusion was performed to establish the maximum-tolerated dose (MTD) and to investigate pharmacokinetics, pharmacodynamics, and antitumor effects. METHODS In vitro and in vivo preclinical studies demonstrated increased activity with prolonged nolatrexed exposure. In 32 patients, nolatrexed was given as a 5-day infusion at 96 to 1,040 mg/m2/d for 5 days. Pharmacokinetics were determined from high-performance liquid chromatography (HPLC) analyses of plasma and urine. In addition to studying toxicity, plasma deoxyuridine (UdR) elevations were measured as a marker of TS inhibition. RESULTS The MTD was 904 mg/m2/d for 5 days and the recommended phase II dose is 800 mg/m2/d for 5 days. The dose-limiting toxicity was neutropenia with clinically significant thrombocytopenia and mucositis. These antiproliferative toxicities of nolatrexed were predictable and reversible. A partial response that lasted 3 months occurred in a patient with metastatic colorectal cancer. Pharmacokinetics were nonlinear, with the median plasma clearance (CI) decreasing from 151 mL/min/m2 (range, 124 to 211) at 96 mg/m2/d for 5 days to 49 mL/min/m2 (range, 30 to 84) at 768 mg/ m2/d for 5 days. The half-life (t1/2) was 173 minutes (range, 43 to 784) and 18% (range, 9% to 35%) of the dose was excreted unchanged in the urine. Plasma UdR increased, but returned to pretreatment levels after the end of infusion. Hematologic toxicity was significantly related to nolatrexed plasma concentrations and dose. CONCLUSION Nolatrexed can be safely administered to patients at a dose of 800 mg/m2/d over 5 days by continuous intravenous infusion and this schedule is associated with antitumor effects. The phase II evaluation of nolatrexed is ongoing.

Phase I trial of panobinostat (P) and imatinib (IM) in patients with treatment-refractory gastrointestinal stromal tumors (GIST).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10032-10032
Author(s):  
Sebastian Bauer ◽  
Ralf A. Hilger ◽  
Florian Grabellus ◽  
James Nagarajah ◽  
Mathias Hoiczyk ◽  
...  
Keyword(s):  
Phase I ◽  
Mononuclear Cells ◽  
Metabolic Response ◽  
Combined Treatment ◽  
Plasma Concentrations ◽  
Maximum Tolerated Dose ◽  
Clinical Activity ◽  
Peripheral Blood Mononuclear

10032^ Background: Panobinostat (LBH589; P) is a pan-deacetylase-inhibitor that has preclinical activity in combination with IM in GIST models in vitro and in vivo. Aim of this study was to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of escalating doses of P in combination with IM in patients with GIST who have failed IM and sunitinib treatment. Methods: This was a two-center phase I study using a 3+3 design with a prespecified expansion of the MTD cohort. IM was administered at a dose of 400mg qd. Following a 7 day run-in phase, escalating doses of P were added. The starting dose for P was 20 mg given as a three-times-per-week (MWF schedule) oral dose for 3 out of 4 weeks. Doses were increased by 10 mg if no dose limiting toxicities emerged. Blood samples were drawn for PK and biomarker assessments of IM, its main metabolite N-desmethyl-IM, and P using a validated RP-HPLC method. Acetylation of histone A3 was evaluated in peripheral blood mononuclear cells (PBMNC) as pharmacodynamic marker for P activity. Metabolic response using PET (EORTC-PET study criteria) was assessed on day 7 of IM run-in and after 3 weeks of combined treatment with IM and P. Results: In total 12 extensively pretreated (median 5 pretreatments) pts (4 f, 8 m; median age 56 y, 34-75 y) received study treatment at 2 dose levels (DL). 2 dose-limiting toxicities (grade 4 thrombocytopenia) occurred at DL 2 (30 mg). Most common AEs were thrombocytopenia, anemia, fatigue, nausea, emesis, diarrhea, creatinine elevation, abdominal cramping, and weight loss. DL 1 (20mg) was declared MTD, and 5 additional pts were enrolled at DL1. Analysis of P and IM PK revealed mean peak concentration of 14.8 +/- 9.5 ng/ml for P (20 mg). IM plasma concentrations with 400 mg once-daily administration were 2.8 ± 1.1 μg/mL at peak and 1.2 ± 0.4 μg/mL at trough. Histone A3 acetylation was demonstrated in PBMNC from pts treated at DL 1. 11 pts were evaluable for PET response: 1 had mPR, 7 had mSD and 3 had mPD. Longest treatment duration was 17 weeks (median: 6wks). Conclusions: P in combination with IM is moderately tolerated. Evidence of target inhibition at the MTD was associated with limited clinical activity in heavily pretreated pts with GIST.

scholarly journals CTNI-78. A PEDIATRIC AND YOUNG ADULT PHASE I DOSE ESCALATION SAFETY STUDY OF BXQ-350 FOR REFRACTORY SOLID AND CENTRAL NERVOUS SYSTEM TUMORS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii60-ii61
Author(s):  
Bhuvana Setty ◽  
Mohamed AbdelBaki ◽  
Mariko DeWire ◽  
Timothy Cripe ◽  
Rich Curry
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Phase I ◽  
Dose Level ◽  
Dose Escalation ◽  
Maximum Tolerated Dose ◽  
Antitumor Effects ◽  
Serious Adverse Events

Abstract BACKGROUND BXQ-350 is a novel agent composed of the multifunctional, lysosomal activator protein Saposin C (SapC) and dioleoyl- phosphatidylserine (DOPS) and has demonstrated antitumor effects in both in vitro and in vivo preclinical models. Many tumors, including high-grade glioma and diffuse intrinsic pontine glioma (DIPG), and cells of tumor vasculature have aberrantly-exposed phosphatidylserine (PS)-rich domains on the cell surface. BXQ-350 is an anti-tumor agent in development from Bexion Pharmaceuticals, Inc. that selectively targets tumor cell PS, particularly those translocated to the outer leaflet of the plasma membrane in tumor cells. BXQ-350 activates and participates in various cellular processes, including apoptosis and necrosis, and may also exhibit novel mechanisms leading to cell death that require further investigation. METHODS Nine refractory solid (2) and central nervous system (7) tumor patients (5F:4M, age 4–23 years of age) were enrolled in a 2-site dose escalation Phase I first-in-pediatric trial (NCT03967093) which completed in 2019. All patients received at least one dose of BXQ-350 which was administered as an intravenous infusion. Dosing began at 1.8 mg/kg and escalated to the highest planned dose level of 3.2mg/kg. RESULTS There were no BXQ-350-related serious adverse events, dose limiting toxicities or withdrawals. The highest planned dose of 3.2 mg/kg was achieved safely but a maximum tolerated dose was not established. One osteosarcoma patient had progressive disease prior to completing cycle one of treatment and was removed from trial. Eight patients (DIPG-3, HGG-1, GBM-1, Pineoblasotoma-1, Ependymoma-1, Osteosarcoma-1) completed at least one cycle, with one DIPG patient completing cycle five. CONCLUSION BXQ-350 was well tolerated with no significant dose-limiting toxicities at the highest planed dose level. A pediatric Phase I trial in newly diagnosed patients is planned for 3rd quarter 2020.

A phase I/II clinical trial of intravenous (I.V.) calcitriol with fixed doses of cisplatin and docetaxel in advanced non-small cell lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18118-e18118
Author(s):  
Nithya Ramnath ◽  
Stephanie Daignault-Newton ◽  
Grace K. Dy ◽  
Josephia Muindi ◽  
Araba Adjei ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Single Agent ◽  
Normal Liver ◽  
Maximum Tolerated Dose ◽  
In Vivo Studies ◽  
Open Label ◽  
Chi Square

e18118 Background: In vitro and in vivo studies have demonstrated the antiproliferative effects of 1, 25 (OH)2D3 (calcitriol) as single agent and antitumor synergy with cisplatin. The goals of this Phase I/II study were to determine the maximum tolerated dose (MTD) of 1, 25 (OH)2 D3 in combination with cisplatin and docetaxel, and to evaluate the efficacy in patients (pts) with metastatic NSCLC.Methods: The study was a multicenter, open-label study in pts with metastatic NSCLC. Pts were adults 18 yrs., PS 0-1 with normal liver/kidney function. For the phase I study, pts (3–6 per cohort) received 1, 25 (OH)2 D3 I.V. every 21 days prior to docetaxel and cisplatin. The starting dose of 1,25 (OH)2D3 was 15 mcg/m2 at sequential ascending dose levels (DL) (15, 30, 60 and 80 mcg/m2) using a 3+3 design targeting a dose-limiting toxicity (DLT) rate of <33%. Docetaxel was administered at 75 mg/m2 and cisplatin 75mg/m2 following 1, 25 (OH)2 D3 for 4 cycles. We analyzed SNPs in the CYP24A1 gene.Results: 37 pts were enrolled (16 in phase I and 21 in phase II) with a median age of 54 (range 34–79) yrs.; M: F, 12:17. At the 80 mcg/m2 dose level, 2/4 pts had DLT of grade 4 neutropenia. There were no cases of hypercalcemia or azotemia. The MTD and recommended Phase II dose was 60 mcg/m2. Among 6 response-evaluable Phase I pts, and 21 phase II pts, there were: 2 confirmed partial responses (PR), 6 unconfirmed PRs and 10 pts with stable disease. The median time to progression was 6.9 months (95% CI 4.4, 12.9) and the median overall survival was 8.3 months (95% CI 5.8, 14.9). Of the CYP24A1 SNPs, the IVS4-308C>G was associated with progressive disease (Chi-Square=0.0062)Conclusions: The MTD of 1,25 (OH)2D3 in combination with docetaxel and cisplatin was 60 mcg/m2 IV every 21 days. Pre-specified endpoint of a 50% response rate was not met in the phase II study. However, disease control in 66% of patients argues for further study of 1,25 (OH)2D3 as maintenance therapy. The CYP24A1 polymorphism IVS4-308C>G may be associated with resistance to a 1,25 (OH)2D3 based therapeutic regimen

Phase I Study of Liposomal Vincristine

1999 ◽  
Vol 17 (2) ◽  
pp. 697-697 ◽  
Author(s):  
K. A. Gelmon ◽  
A. Tolcher ◽  
A. R. Diab ◽  
M. B. Bally ◽  
L. Embree ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase I ◽  
Phase Ii ◽  
Phase I Study ◽  
High Performance ◽  
Clinical Investigation ◽  
Maximum Tolerated Dose ◽  
Pharmacokinetic Studies ◽  
Hematologic Toxicity ◽  
Chromatography Method

PURPOSE: A phase I study of vincristine encapsulated inside 120-nm-diameter distearoylphosphatidylcholine-cholesterol liposomes was performed. The primary objectives were to determine the maximum-tolerated dose (MTD), recommended phase II dose, toxicity, and pharmacokinetics of liposomal vincristine (ONCO-TCS). PATIENTS AND METHODS: Twenty-five patients with histologically confirmed malignancies were enrolled and assessable. Vincristine doses were increased from 0.5 mg/m2 to 1.0, 1.5, 2.0, 2.4, and 2.8 mg/m2 with cohorts of three or more patients per dose level. A total of 64 courses of ONCO-TCS were administered intravenously once every 3 weeks. The pharmacokinetics of total vincristine content in plasma were determined using a high-performance liquid chromatography method. RESULTS: Patients were treated with vincristine doses up to 2.8 mg/m2; however, 2.4 mg/m2 was defined as the MTD and 2.0 mg/m2 as the phase II recommended dose. Pain and obstipation were the dose-limiting toxicites. Other toxicities were fever, rigors, fatigue, myalgias, and peripheral neuropathy. Hematologic toxicity was mild. All patients who were treated with doses above 1.5 mg/m2 received in excess of 2.0 mg of vincristine, with doses as high as 6.2 mg. One partial response was seen in a patient with pancreatic cancer. Tumor response not meeting partial response criteria was seen in two other patients. Pharmacokinetic studies revealed significantly elevated concentrations of total vincristine, but parameters varied and were not directly correlated with toxicity or response. CONCLUSION: The ability to administer elevated doses of vincristine, as well as indications of efficacy, suggests that ONCO-TCS warrants further clinical investigation in a phase II setting.

Effects of Ofloxacin Administration on the Reliability of Urine Glucose Testing

1996 ◽  
Vol 30 (5) ◽  
pp. 469-472
Author(s):  
Tsong-Mei Tsai ◽  
Brian F Shea ◽  
Paul F Souney ◽  
Fred G Volinsky ◽  
Joseph M Scavone ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Tertiary Care ◽  
Urine Samples ◽  
Care Hospital ◽  
Open Label ◽  
Urine Glucose ◽  
Glucose Testing

OBJECTIVE: TO study the effects of ofloxacin on the reliability of urine glucose testing. DESIGN: Open-label, nonrandomized. SETTING: A university-affiliated tertiary care hospital, ambulatory clinic. PARTICIPANTS: Ten healthy volunteers (8 men and 2 women) aged 22-39 years. MAIN OUTCOME MEASURES: Phase I (in vitro) involved the addition of selected amounts of ofloxacin to a set of standard 50-mL urine samples prepared to simulate glycosuria. Phase II (in vivo) involved the oral administration of ofloxacin 400 mg to 10 subjects. Urine was collected: (1) immediately predose, (2) pooled 0–4 hours postdose, and (3) pooled 4–8 hours postdose. Known glucose concentrations were then added to these samples. Clinitest and Diastix tests were performed on all samples. The accuracy of these tests in determining glucose concentrations was compared among urine samples taken before and after ofloxacin dosing. RESULTS: None of the ofloxacin concentrations in phase I (0,25,50, 100, 200,400, and 800 μg/mL) influenced these testing methods at the urine glucose concentrations of 0.0%, 0.5%, 1%, and 2%. Likewise, the accuracy of these two tests was unaffected by ofloxacin administration in phase II. CONCLUSIONS: In single-dose administration, ofloxacin does not interfere with Clinitest or Diastix for determining urine glucose concentrations. Supported by a grant from the RW Johnson Pharmaceutical Research Institute. Presented in abstract form at the American College of Clinical Pharmacy 1994 Winter Practice and Research Forum, February 6–9, 1994, San Diego. CA.

scholarly journals Serotherapy of B-cell neoplasms with anti-B4-blocked ricin: a phase I trial of daily bolus infusion

Blood ◽  
1992 ◽  
Vol 79 (3) ◽  
pp. 576-585 ◽  
Author(s):  
ML Grossbard ◽  
AS Freedman ◽  
J Ritz ◽  
F Coral ◽  
VS Goldmacher ◽  
...  
Keyword(s):  
Phase I ◽  
B Cell ◽  
Maximum Tolerated Dose ◽  
In Vitro Cytotoxicity ◽  
Bolus Infusion ◽  
Protein Toxin ◽  
Cytotoxicity Studies ◽  
Ricin A

Anti-B4-blocked Ricin (Anti-B4-bR) is an immunotoxin comprised of the anti-B4 monoclonal antibody (MoAb) and the protein toxin “blocked ricin.” The anti-B4 MoAb is directed against the B-lineage-restricted CD19 antigen expressed on more than 95% of normal and neoplastic B cells. Blocked ricin is an altered ricin derivative that has its nonspecific binding eliminated by chemically blocking the galactose binding domains of the B chain. In vitro cytotoxicity studies demonstrate that the IC37 of Anti-B4-bR is 2 x 10(-11) mol/L compared with 4 x 10(-12) mol/L for native ricin. A phase I dose escalation clinical trial was conducted in 25 patients with refractory B-cell malignancies. Anti-B4-bR was administered by daily 1-hour bolus infusion for 5 consecutive days at doses ranging from 1 microgram/kg/d to 60 micrograms/kg/d. Serum levels above 1 nmol/L were achieved transiently in the majority of patients treated at the maximum tolerated dose of 50 micrograms/kg/d for 5 days for a total dose of 250 micrograms/kg. The dose-limiting toxicity was defined by transient, reversible grade 3 elevations in hepatic transaminases, without impaired hepatic synthetic function. Minor toxicities included transient hypoalbuminemia, thrombocytopenia, and fevers. Human antimouse antibody and human anti-ricin antibody were detected in nine patients. One complete response, two partial responses, and eight mixed or transient responses were observed. These results show the in vitro and in vivo cytotoxicity of Anti-B4-bR and indicate that this immunotoxin can be administered as a daily bolus infusion for 5 days with tolerable, reversible toxicity.

scholarly journals First-in-human phase I trial of anti-hepatocyte growth factor antibody (YYB101) in refractory solid tumor patients

2020 ◽  
Vol 12 ◽  
pp. 175883592092679
Author(s):  
Seung Tae Kim ◽  
Jung Yong Hong ◽  
Se Hoon Park ◽  
Joon Oh Park ◽  
Young Whan Park ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Phase I ◽  
Cancer Patients ◽  
Phase I Trial ◽  
Maximum Tolerated Dose ◽  
Safety And Efficacy ◽  
Hepatocyte Growth

Background: YYB101, a humanized monoclonal antibody against hepatocyte growth factor (HGF), has shown safety and efficacy in vitro and in vivo. This is a first-in-human trial of this antibody. Materials and Methods: YYB101 was administered intravenously to refractory cancer patients once every 4 weeks for 1 month, and then once every 2 weeks until disease progression or intolerable toxicity, at doses of 0.3, 1, 3, 5, 10, 20, 30 mg/kg, according to a 3+3 dose escalation design. Maximum tolerated dose, safety, pharmacokinetics, and pharmacodynamics were studied. HGF, MET, PD-L1, and ERK expression was evaluated for 9 of 17 patients of the expansion cohort (20 mg/kg). Results: In 39 patients enrolled, no dose-limiting toxicity was observed at 0.3 mg/kg, and the most commonly detected toxicity was generalized edema ( n = 7, 18.9%) followed by pruritis and nausea ( n = 5, 13.5%, each), fatigue, anemia, and decreased appetite ( n = 4, 10.8%, each). No patient discontinued treatment because of adverse events. YYB101 showed dose-proportional pharmacokinetics up to 30 mg/kg. Partial response in 1 (2.5%) and stable disease in 17 (43.5%) were observed. HGF, MET, PD-L1, and ERK proteins were not significant predictors for treatment response. However, serum HGF level was significantly lowered in responders upon drug administration. RNA sequencing revealed a mesenchymal signature in two long-term responders. Conclusion: YYB101 showed favorable safety and efficacy in patients with refractory solid tumors. Based on this phase I trial, a phase II study on the YYB101 + irinotecan combination in refractory metastatic colorectal cancer patients is planned. Conclusion: ClinicalTrials.gov Identifier: NCT02499224

Phase I and Pharmacokinetic Study of the Camptothecin Analog DX-8951f Administered as a 30-Minute Infusion Every 3 Weeks in Patients With Advanced Cancer

2000 ◽  
Vol 18 (23) ◽  
pp. 3986-3992 ◽  
Author(s):  
Valérie Boige ◽  
Eric Raymond ◽  
Sandrine Faivre ◽  
Michel Gatineau ◽  
Kathleen Meely ◽  
...  
Keyword(s):  
Phase I ◽  
Intravenous Infusion ◽  
Topoisomerase I ◽  
High Performance ◽  
Plasma Concentrations ◽  
Maximum Tolerated Dose ◽  
Pharmacokinetic Analysis ◽  
Phase Ii Studies ◽  
Heavily Pretreated ◽  
Dose Limiting Toxicity

PURPOSE: DX-8951f is a totally synthetic derivative of camptothecin with greater cytotoxicity and more potent topoisomerase I inhibition than SN-38, topotecan, and camptothecin in preclinical studies. This phase I study aimed to describe the toxicity and to determine the maximum-tolerated dose (MTD) and pharmacokinetics of DX-8951f given as a 30-minute intravenous infusion every 3 weeks. PATIENTS AND METHODS: Twelve patients with refractory solid malignancies were treated with DX-8951f at dose levels ranging from 4 to 7.1 mg/m2. All but one patient had received previous chemotherapy, and eight patients were considered heavily pretreated. Total DX-8951f plasma concentrations were assayed using high-performance liquid chromatography. RESULTS: Thirty-six cycles of DX-8951f were administered. Neutropenia was the dose-limiting toxicity, and it was dose-related, reversible, and noncumulative. Other toxicities included nausea and vomiting, alopecia, asthenia, fever, and anemia. Grade 1 or 2 diarrhea was observed in seven patients but was transient and resolved without requiring treatment. Pharmacokinetic analysis showed that DX-8951f had a half-life of 7.15 hours and a clearance rate of 1.65 L/h·m2. The DX-8951f area under the plasma-concentration curve increased linearly with the dose. We defined the MTD of DX-8951f administered as a 30-minute intravenous infusion every 3 weeks as 7.1 mg/m2. CONCLUSION: The dose-limiting toxicity of DX-8951f is neutropenia. The recommended dose for phase II studies is 5.33 mg/m2 every 3 weeks in patients previously treated with chemotherapy.

Gas Chromatographic Determination of Poly chlorinated Biphenyls (as Aroclor 1254) in Serum: Collaborative Study

1989 ◽  
Vol 72 (4) ◽  
pp. 649-659
Author(s):  
Virlyn W Burse ◽  
Margaret P Korver ◽  
Larry L Needham ◽  
Chester R Lapeza ◽  
Elizabeth L Chester R ◽  
...  
Keyword(s):  
Phase I ◽  
Silica Gel ◽  
Phase Ii ◽  
Collaborative Study ◽  
Chlorinated Hydrocarbons ◽  
Aroclor 1254 ◽  
Relative Standard

Abstract A gas chromatographic-electron capture detection method for determining the concentration of polychlorinated biphenyls (PCBs) as Aroclor 1254 (AR 1254) in serum was evaluated through a 2-phase collaborative study. In Phase I, each collaborator's lot of Woelm silica gel (70-150 mesh) was evaluated for elution and recovery of AR 1254, which had been added in vitro at 25 ng/mL to a serum extract. In Phase II, each collaborator analyzed a series of bovine serum samples that contained the following: (1) in vitro-spiked AR 1254; (2) in vivo AR 1254 and 8 in vitro-spiked chlorinated hydrocarbons; (3) in vivo AR 1254 only; (4) 8 in vitro-spiked chlorinated hydrocarbons only; and (5) neither AR 1254 nor chlorinated hydrocarbons above the detection limit of the method. In Phase I, the average recovery of AR 1254 from silica gel for the 6 collaborators was 87.9 ± 15.44% (mean ± 1 SD; N = 18; range = 52.3-105.8%). In Phase II, the analysis of in vitro spikes of AR 1254 in serum at 8.58,16.8, 41.8, and 84.3 ppb gave mean (X) interlaboratory recoveries of 89.0, 83.3, 79.4, and 76.9%, respectively, with within-laboratory (repeatability) relative standard deviations (RSDr) of 18.8, 20.5, 10.2, and 14.1%, respectively, and among-laboratory (reproducibility) relative standard deviations (RSDR) of 21.5, 21.1, 14.6, and 20.8%, respectively. The determination of in vivo AR 1254 in samples containing approximately 10, 25, 50, and 100 ng/mL of AR 1254 resulted in interlaboratory means of 10,22,39, and 79 ng/mL, respectively, with RSDr = 6.7,9.7,6.4, and 5.8%, respectively, and RSDR = 20.6,16.0, 10.9, and 10.3%, respectively. The precision of the method for incurred AR 1254 showed a maximum RSDr of less than 10% and a maximum RSDR of less than 21% for a concentration range of 10-100 ng/mL. The accuracy of the method as demonstrated by the mean recovery of in vitro-spiked AR 1254 over a concentration range of 8.58-84.3 ng/mL was 82.2%. The method has been approved interim official first action.

Sign in / Sign up

Export Citation Format

Share Document